Anti-Infective Compounds

ABSTRACT

The present invention relates to small molecule compounds having the general formula (I): wherein A is a moiety selected from the group consisting of formulae (A) to (K) and their use in the treatment of bacterial infections, in particular Tuberculosis.

The present invention relates to small molecule compounds and their usein the treatment of bacterial infections, in particular Tuberculosis.

BACKGROUND OF THE INVENTION

Tuberculosis (TB) still claims the life of more than 1.8 million peopleeach year. Inadequate use of chemotherapy has led to an increasingnumber of multi-drug resistant (MDR) TB, and the situation is likely toworsen with the emergence and spread of extensively drug resistant formsof the disease (Chaisson R. E. & Nuermberger E. L., N Engl J Med 2012).The most urgent clinical need is to discover potent agents capable ofreducing the time of M/XDR tuberculosis therapy with a success ratecomparable to susceptible tuberculosis. The last decade has seen thediscovery of promising new agent classes for the management oftuberculosis (Stover C. K. et al. Nature 2000; Andreis K. et al. Science2005), several of which are currently under clinical development (DiaconA. H. et al. Antimicrob Agents Chemother 2012; Gler M. T. et al. N EnglJ Med 2012). However, given the high attrition rate during clinicaldevelopment and the emergence of resistance, the discovery of additionalclinical candidates is clearly needed.

Current chemotherapy consists of compounds that directly targetMycobacterium tuberculosis bacillus, by targeting either the synthesisof macromolecules such as DNA, RNA or protein synthesis, or keycomponents of the cell-wall. The most widely used dedicatedanti-tubercular drugs isoniazid, ethionamide and pyrazinamide arepro-drugs that first require activation. As active forms, theydemonstrate inhibitory activity on primarily cell-wall synthesis and/oron a wide range of mycobacterial targets, which have not yet been fullycharacterized.

One of the most challenging obstacles in the discovery of new anti-TBdrugs is the lack of predictive in vitro screening methods thatreproduce critical features found in vivo. Although there is still alack of understanding of the biological mechanisms behind tuberclebacillus persistence, i.e. the location and state of latent bacteria inhumans, M. tuberculosis is thought to persists in primary granulomas andwithin various cell types (Houben et al., 2006; Neyrolles et al., 2006).The bacillus mainly localizes inside phagocytic cells, such asmacrophages and dendritic cells, where it adapts drastically itsmetabolism to survive the harsh environment found in professionalphagocytic cells (Rohde et al., 2007). Therefore, we developed and useda phenotypic high-content screening technology in infected macrophagesto identify novel antitubercular compounds (WO2010003533A2), overcomingmany of the numerous and burdensome steps involved with othermethodologies (Arain et al., 1996). The technology has severaladvantages compared to traditional phenotypic screening approaches sinceit allows i) screening under physiologically relevant conditions, whichis notoriously challenging in the field (Stanley S. A. et al., ACS ChemBiol 2012), ii) selection of non-cytotoxic compounds that penetrateeffectively inside macrophages (Pethe K. et al. Nat Med. 2013), and iii)selection of compounds that are poor substrates for macrophage-inducedefflux mechanisms, thereby compressing the discovery and optimizationtime of new lead molecules.

It was an object of the present invention to identify compoundseffective against bacterial infections, in particular compounds thatwould prevent M. tuberculosis multiplication inside the host macrophage.

DESCRIPTION OF THE INVENTION

In one aspect, the present invention relates to compounds having thegeneral formula I:

whereinn¹ and n² are independently 0, 1, 2, or 3;in is 0 or 1;A is a moiety selected from the group consisting of

R¹ is selected from the group consisting of hydrogen, halogen, C₁-C₁₀alkyl, C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl, hydroxyl, —OR³, —CN, —NO₂,—NH₂, —NR^(b)R^(c), aryl, heteroaryl and heterocyclyl group wherein eachof said alkyl, cycloalkyl, aryl heteroaryl and heterocyclyl isoptionally substituted with one to four R^(a) groups;R² is selected from the group consisting of hydrogen, halogen, C₁-C₁₀alkyl, C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl, hydroxyl, —OR³, —CN, —NO₂,—NH₂, —NR^(b)R^(c), —NR⁶C(O)R^(c), —(NR^(d))(V)_(p)R^(e), aryl,heteroaryl, heterocyclyl group and groups of formula Ia shown below,wherein each of said alkyl, cycloalkyl, aryl, heteroaryl andheterocyclyl is optionally substituted with one to four R^(a) groups;

wherein,o is independently, at each occurrence, 0, 1, 2 or 3;p is 0 or 1,q is 0 or 1;X¹ is C═O, O, S, —S(O)₂—, —S(O)₂NR⁶—, —C(O)O—, —C(O)NR⁶—, —NHC(O)— or—(NR⁶)—;X² is selected from CR^(b)R^(c), O, S, or NR⁶;Y is C₁-C₆ alkylene, O, S or NR⁶;V and W are independently, at each occurrence, C₁-C₆ alkylene;R³ is selected from the group consisting of hydrogen, C₁-C₁₀ alkyl,C₃-C₁₀cycloalkyl, C₁-C₁₀ haloalkyl in particular, C₁-C₃haloalkyl,C₁-C₆alkyl-O-alkyl, C₂-C₁₀ alkenyl, C₃-C₁₀ cycloalkenyl, C₂-C₁₀ alkynyl,aryl, heteroaryl and heterocyclyl group, wherein each of said alkyl,cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substitutedwith one to four R^(a) groups;R⁴ is selected from the group consisting of hydrogen, halogen, C₁-C₁₀alkyl, C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl, hydroxyl, —OR⁶, —CN, —NO₂,—NH₂, —NR^(b)R^(c), —N(R⁶)C(O)R⁶, —C(O)R⁶, —C(O)OR⁶, —C(O)NR^(b)R^(c),—S(O)R⁶, —S(O)₂R⁶, —S(O)₂NR^(b)R^(c), aryl, heteroaryl and heterocyclylgroup wherein each of said alkyl, cycloalkyl, —OR⁶ aryl, heteroaryl andheterocyclyl is optionally substituted with one to four R^(a) groups;R⁵ is selected from the group consisting of hydrogen, halogen, C₁-C₁₀alkyl, C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl, hydroxyl, —OR⁶, —CN, —NO₂,—NH₂, —NR^(b)R^(c), —N(R⁶)C(O)R⁶, —N(R⁶)C(O)OR⁶, —C(O)R⁶, —C(O)OR⁶,—C(O)NR^(b)R^(c), —CHOHR⁶, —S(O)R⁶, —S(O)₂R⁶, —S(O)₂NR^(b)R^(c), aryl,e.g. phenyl, benzyl, heteroaryl and heterocyclyl group wherein each ofsaid alkyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl is optionallysubstituted with one to four R^(a) groups;R⁶ is independently, at each occurrence, selected from the groupconsisting of hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl,aryl, heteroaryl and heterocyclyl group, wherein each of said alkyl,cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substitutedwith one to four R^(a) groups;Z is selected from the group consisting of C₁-C₁₀ alkyl,C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl, OR⁷, aryloxy, aryl, e.g. phenyl orbenzyl, heteroaryl, heterocyclyl group, e.g. piperidinyl, morpholinyl,and groups of formula Ib shown below, wherein each of said alkyl,cycloalkyl, aryl, heteroaryl, heterocyclyl and groups of formula Ib isoptionally substituted with one to four R^(a) groups;

wherein,p is 0 or 1;l is 1, 2 or 3;X³ is, independently at each occurrence, selected from CH or N;X⁴ is selected from C═O, CR^(b)R^(c), O, S, or NR⁷;R^(e), if denoted in formula Ib, may also occur twice as substituent atthe same carbon atom wherein R^(e) is independently selected at eachoccurrence;R^(a) is independently, at each occurrence, selected from the groupconsisting of hydrogen, halogen, C₁-C₃ alkyl, C₁-C₄ alkoxy, C₁-C₄ alkoxysubstituted with aryl, e.g. phenyl or benzyl, aryloxy; C₁-C₃ haloalkyl,hydroxyl, C₁-C₃ alkylhydroxyl, —CN, NO₂, —NR^(b)R^(c), —C(O)NR^(b)R^(c),—OR^(c), —C(O)R^(c), —C(O)OR^(c), sulfonyl, sulfoxide, C₃-C₁₀cycloalkyl, heterocyclyl, heteroaryl and aryl, e.g. phenyl, benzyl,alkylaryl wherein each of said alkyl, cycloalkyl, aryl, heteroaryl andheterocyclyl is optionally substituted with one to four C₁-C₃ alkyl,C₁-C₄ alkoxy, aryl, e.g. phenyl, benzyl, halogen, C₁-C₃ haloalkyl,hydroxyl, —NH₂, wherein such substitution, if present, may occur in sucha manner that there is more than one substituent, e.g. two or threesubstituents, per carbon atom, wherein these two or three substituentsmay be the same or different;R^(b) and R^(c) are independently, at each occurrence selected from thegroup consisting of hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₆alkyl-O-alkyl, C₂-C₁₀ alkenyl, C₁-C₄ alkoxy, C₁-C₃ alkylhydroxyl, C₃-C₁₀cycloalkenyl, C₂-C₁₀ alkynyl, haloalkyl, in particular C₁-C₃ haloalkyl,aryl, e.g. phenyl or benzyl, alkylaryl, heteroaryl, and heterocyclyl,wherein each of said alkyl, cycloalkyl, aryl, heteroaryl andheterocyclyl is optionally substituted with one to four C₁-C₃ alkyl,C₁-C₄ alkoxy, e.g. methoxy, halogen, aryloxy, C₁-C₃ haloalkyl, e.g.trifluoromethyl, hydroxyl, C₁-C₃ alkylhydroxyl, —CN, —NO₂, —NH₂,sulfonyl, sulfoxide, C₃-C₁₀ cycloalkyl, heterocyclyl, aryl, e.g. phenyl,benzyl, heteroaryl, wherein such substitution, if present, may occur insuch a manner that there is more than one substituent, e.g. two or threesubstituents, per carbon atom, wherein such two or three substituentsmay be the same or different; orR^(b) and R^(c) are connected to each other to make a four, five or sixmembered saturated or unsaturated cyclic or heterocyclic ring, or theyare connected to make a fused cyclic or heterocyclic ring structure;R^(d) is independently, at each occurrence, selected from the groupconsisting of hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl,aryl, e.g. phenyl or benzyl, heteroaryl and heterocyclyl group, whereineach of said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl isoptionally substituted with one to four R^(a) groups;R^(e) is independently, at each occurrence, selected from the groupconsisting of hydrogen, halogen, C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl,C₁-C₃haloalkyl, hydroxyl, —OR⁷, —CN, —(CH₂)_(l)R⁷, with l being 0, 1, 2or 3, —NO₂, —NH₂, —NR^(b)R^(c), —N(R⁷)C(O)R⁷, —C(O)R⁷, —C(O)OR⁷,—C(O)NR^(b)R^(c), —S(O)R⁷, —S(O)₂R⁷, —S(O)₂NR^(b)R^(c), aryl, e.g.phenyl or benzyl, heteroaryl and heterocyclyl group, wherein each ofsaid alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionallysubstituted with one to four R^(a) groups;R⁷ is independently, at each occurrence, selected from the groupconsisting of hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃haloalkyl, aryl, e.g. phenyl or benzyl, heteroaryl, and heterocyclyl,wherein each of said alkyl, cycloalkyl, aryl, heteroaryl andheterocyclyl is optionally substituted with one to four R^(a) groups,and pharmaceutically acceptable salts thereof.

In one embodiment, the compound has the general formula II:

whereinn is 0, 1, 2 or 3;m is 0 or 1;o is 0, 1, 2 or 3;X² is selected from CR^(b)R^(c), O, S, or NR⁶;Y is C₁-C₆ alkylene, O, S or NR⁶;R⁴ is selected from the group consisting of hydrogen, halogen, C₁-C₁₀alkyl, C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl, hydroxyl, —OR⁶, —CN, —NO₂,—NH₂, —NR^(b)R^(c), —N(R⁶)C(O)R⁶, —C(O)R⁶, —C(O)OR⁶, —C(O)NR^(b)R^(c),—S(O)R⁶, —S(O)₂R⁶, —S(O)₂NR^(b)R^(c), aryl, e.g. phenyl or benzyl,heteroaryl and heterocyclyl group wherein each of said alkyl,cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substitutedwith one to four R^(a) groups;R⁶ is independently, at each occurrence, selected from the groupconsisting of hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl,aryl, e.g. phenyl or benzyl, heteroaryl and heterocyclyl group, whereineach of said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl isoptionally substituted with one to four R^(a) groups;Z is selected from the group consisting of C₁-C₁₀ alkyl,C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl, OR⁶, aryloxy, aryl, e.g. phenyl orbenzyl, heteroaryl, heterocyclyl group, and groups of formula Ib shownbelow, wherein each of said alkyl, cycloalkyl, aryl, heteroaryl,heterocyclyl and groups of formula Ib is optionally substituted with oneto four R^(a) groups;

wherein,p is 0 or 1;l is 1, 2 or 3;X³ is, independently at each occurrence, selected from CH or N;X⁴ is selected from C═O, CR^(b)R^(c), O, S, or NR⁷;R^(e), if denoted in formula Ib, may also occur twice as substituent atthe same carbon atom wherein R^(e) is independently selected at eachoccurrence;R^(a) is independently, at each occurrence, selected from the groupconsisting of hydrogen, halogen, C₁-C₃ alkyl, C₁-C₄ alkoxy, C₁-C₄ alkoxysubstituted with aryl, e.g. phenyl, benzyl, aryloxy; C₁-C₃ haloalkyl,hydroxyl, C₁-C₃ alkylhydroxyl, —CN, NO₂, —NR^(b)R^(c),—C(O)NR^(b)R^(c),—OR^(c), —C(O)R^(c), —C(O)OR^(c), sulfonyl, sulfoxide,C₃-C₁₀ cycloalkyl, heterocyclyl, heteroaryl and aryl, e.g. phenyl orbenzyl, alkylaryl wherein each of said alkyl, cycloalkyl, aryl,heteroaryl and heterocyclyl is optionally substituted with one to fourC₁-C₃ alkyl, C₁-C₄ alkoxy, aryl, e.g. phenyl or benzyl, halogen, C₁-C₃haloalkyl, hydroxyl, —NH₂ wherein such substitution, if present, mayoccur in such a manner that there is more than one substituent, e.g. twoor three substituents, per carbon atom, wherein such two or threesubstituents may be the same or different;R^(b) and R^(c) are, independently at each occurrence, selected from thegroup consisting of hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₆alkyl-O-alkyl, C₂-C₁₀ alkenyl, C₁-C₄ alkoxy, C₁-C₃ alkylhydroxyl, C₃-C₁₀cycloalkenyl, C₂-C₁₀ alkynyl, C₁-C₁₀ haloalkyl, in particular C₁-C₃haloalkyl, aryl, e.g. phenyl or benzyl, alkylaryl, heteroaryl, andheterocyclyl, wherein each of said alkyl, cycloalkyl, aryl, heteroaryland heterocyclyl is optionally substituted with one to four C₁-C₃ alkyl,C₁-C₄ alkoxy, e.g. methoxy, halogen, aryloxy, C₁-C₃ haloalkyl, e.g.trifluoromethyl, hydroxyl, C₁-C₃ alkylhydroxyl, —CN, —NO₂, —NH₂,sulfonyl, sulfoxide, C₃-C₁₀ cycloalkyl, heterocyclyl, aryl, e.g. phenyl,benzyl, heteroaryl, wherein such substitution, if present, may occur insuch a manner that there is more than one substituent, e.g. two or threesubstituents, per carbon atom, wherein such two or three substituentsmay be the same or different or they are connected to make a fusedcyclic or heterocyclic ring structure; orR^(b) and R^(c) are connected to each other to make a four, five or sixmembered saturated or unsaturated cyclic or heterocyclic ring, or theyare connected to make a fused cyclic or heterocyclic ring structure;R^(e) is independently, at each occurrence, selected from the groupconsisting of hydrogen, halogen, C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl,C₁-C₃haloalkyl, hydroxyl, —OR⁷, —CN, —(CH₂)_(l)R⁷ with l being 0, 1, 2or 3, —NO₂, —NH₂, —NR^(b)R^(c), —N(R⁷)C(O)R⁷, —C(O)R⁷, —C(O)OR⁷,—C(O)NR^(b)R^(c), —S(O)R⁷, —S(O)₂R⁷, —S(O)₂NR^(b)R^(c), aryl, heteroaryland heterocyclyl group, wherein each of said alkyl, cycloalkyl, aryl,heteroaryl and heterocyclyl is optionally substituted with one to fourR^(a) groups;R⁷ is independently, at each occurrence, selected from the groupconsisting of hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃haloalkyl, aryl, heteroaryl and heterocyclyl, wherein each of saidalkyl, cycloalkyl, aryl and heterocyclyl is optionally substituted withone to four R^(a) groups, and pharmaceutically acceptable salts thereof.

In one embodiment, the compound has the general formula III:

whereinn is 0, 1, 2 or 3;m is 0 or 1;o is 0, 1, 2 or 3;q is 0 or 1;X² is selected from CR^(b)R^(c), O, S, or NR⁶;Y is C₁-C₆ alkylene, O, S or NR⁶;W is C₁-C₆ alkylene;R⁵ is selected from the group consisting of hydrogen, halogen, C₁-C₁₀alkyl, C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl, hydroxyl, —OR⁶, —CN, —NO₂,—NH₂, —NR^(b)R^(c), —N(R⁶)C(O)R⁶, —N(R⁶)C(O)OR⁶, —C(O)R⁶, —C(O)OR⁶,—C(O)NR^(b)R^(c), —CHOHR⁶, —S(O)R⁶, —S(O)₂R⁶, —S(O)₂NR^(b)R^(c), aryl,e.g. phenyl or benzyl, heteroaryl and heterocyclyl group wherein each ofsaid alkyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl is optionallysubstituted with one to four R^(a) groups;R⁶ is independently, at each occurrence, selected from the groupconsisting of hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl,aryl, e.g. phenyl or benzyl, heteroaryl and heterocyclyl group, whereineach of said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl isoptionally substituted with one to four R^(a) groups;R⁸ is selected from the group consisting of hydrogen, halogen, C₁-C₁₀alkyl, C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl, hydroxyl, —OR⁹, —CN, —NO₂,—NH₂, aryl, e.g. phenyl or benzyl, heteroaryl and heterocyclyl groupwherein each of said alkyl, cycloalkyl, aryl, heteroaryl andheterocyclyl is optionally substituted with one to four R^(a) groups;R⁹ is selected from the group consisting of C₁-C₁₀ alkyl,C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl, aryl, e.g. phenyl or benzyl,heteroaryl and heterocyclyl group wherein each of said alkyl,cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substitutedwith one to four R^(a) groups;Z is selected from the group consisting of C₁-C₁₀ alkyl,C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl, OR⁶, aryloxy, aryl, e.g. phenyl orbenzyl, heteroaryl, heterocyclyl group, and groups of formula Ib shownbelow, wherein each of said alkyl, cycloalkyl, aryl, heteroaryl,heterocyclyl and groups of formula Ib is optionally substituted with oneto four R^(a) groups;

wherein,p is 0 or 1;l is 1, 2 or 3;X³ is, independently at each occurrence, selected from CH or N;X⁴ is selected from C═O, CR^(b)R^(c), O, S, or NR⁷;R^(e), if denoted in formula Ib, may also occur twice as substituent atthe same carbon atom wherein R^(e) is independently selected at eachoccurrence;R^(a) is independently, at each occurrence, selected from the groupconsisting of hydrogen, halogen, C₁-C₃ alkyl, C₁-C₄ alkoxy, C₁-C₄ alkoxysubstituted with aryl, e.g. phenyl, aryloxy; C₁-C₃ haloalkyl, hydroxyl,C₁-C₃ alkylhydroxyl, —CN, NO₂, —NR^(b)R^(c), —C(O)NR^(b)R^(c),—C(O)R^(c), —C(O)OR^(e), sulfonyl, sulfoxide, C₃-C₁₀ cycloalkyl,heterocyclyl, heteroaryl and aryl, e.g. phenyl or benzyl, benzyl,alkylaryl wherein each of said alkyl, cycloalkyl, aryl, heteroaryl andheterocyclyl is optionally substituted with one to four C₁-C₃ alkyl,C₁-C₄ alkoxy, halogen, C₁-C₃ haloalkyl, hydroxyl, —NH₂ wherein suchsubstitution, if present, may occur in such a manner that there is morethan one substituent, e.g. two or three substituents, per carbon atom,wherein such two or three substituents may be the same or different;R^(b) and R^(c) are independently, at each occurrence, selected from thegroup consisting of hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₆alkyl-O-alkyl, C₂-C₁₀ alkenyl, C₁-C₄ alkoxy, C₁-C₃ alkylhydroxyl, C₃-C₁₀cycloalkenyl, C₂-C₁₀ alkynyl, C₁-C₁₀ haloalkyl, in particular C₁-C₃haloalkyl, aryl, e.g. phenyl or benzyl, alkylaryl, heteroaryl, andheterocyclyl; wherein each of said alkyl, cycloalkyl, aryl, heteroaryland heterocyclyl is optionally substituted with one to four C₁-C₃ alkyl,C₁-C₄ alkoxy, e.g. methoxy, halogen, aryloxy, C₁-C₃ haloalkyl, e.g.trifluoromethyl, hydroxyl, C₁-C₃ alkylhydroxyl, —CN, —NO₂, —NH₂,sulfonyl, sulfoxide, C₃-C₁₀ cycloalkyl, heterocyclyl, aryl, e.g. phenyl,benzyl, heteroaryl, wherein such substitution, if present, may occur insuch a manner that there is more than one substituent, e.g. two or threesubstituents, per carbon atom, wherein such two or three substituentsmay be the same or different; orR^(b) and R^(c) are connected to each other to make a four, five or sixmembered saturated or unsaturated cyclic or heterocyclic ring, or theyare connected to make a fused cyclic or heterocyclic ring structure;R^(e) is independently, at each occurrence, selected from the groupconsisting of hydrogen, halogen, C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl,C₁-C₃haloalkyl, hydroxyl, —OR⁷, —CN, —(CH₂)_(l)R⁷ with l being 0, 1, 2or 3, —NO₂, —NH₂, —NR^(b)R^(c), —N(R⁷)C(O)R⁷, —C(O)R⁷, —C(O)OR⁷,—C(O)NR^(b)R^(c), —S(O)R⁷, —S(O)₂R⁷, —S(O)₂NR^(b)R^(c), aryl, e.g.phenyl or benzyl, heteroaryl and heterocyclyl group, wherein each ofsaid alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionallysubstituted with one to four R^(a) groups;R⁷ is independently, at each occurrence, selected from the groupconsisting of hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃haloalkyl, aryl, e.g. phenyl or benzyl, heteroaryl, and heterocyclyl,wherein each of said alkyl, cycloalkyl, aryl, heteroaryl andheterocyclyl is optionally substituted with one to four R^(a) groups,and pharmaceutically acceptable salts thereof.

In one embodiment, the compound has the general formula IV:

whereinn is 0, 1, 2 or 3;m is 0 or 1;V is C₁-C₆ alkyleneR¹⁰ and R^(d) are independently at each occurrence, selected from thegroup consisting of hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl,C₁-C₃haloalkyl, aryl, heteroaryl and heterocyclyl group, wherein each ofsaid alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionallysubstituted with one to four R^(a) groups;R^(e) is independently, at each occurrence, selected from the groupconsisting of hydrogen, halogen, C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl,C₁-C₃haloalkyl, hydroxyl, —OR⁷, —CN, —(CH₂)_(l)R⁷ with l being 0, 1, 2or 3, —NO₂, —NH₂, —NR^(b)R^(c), —N(R⁷)C(O)R⁷, —C(O)R⁷, —C(O)OR⁷,—C(O)NR^(b)R^(c), —S(O)R⁷, —S(O)₂R⁷, —S(O)₂NR^(b)R^(c), aryl, heteroaryland heterocyclyl group, wherein each of said alkyl, cycloalkyl, aryl,e.g. phenyl or benzyl, heteroaryl and heterocyclyl is optionallysubstituted with one to four R^(a) groups;R⁷ is independently, at each occurrence, selected from the groupconsisting of hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl,aryl, heteroaryl and heterocyclyl group, wherein each of said alkyl,cycloalkyl, aryl, e.g. phenyl or benzyl, heteroaryl and heterocyclyl isoptionally substituted with one to four R^(a) groups;Z is selected from the group consisting of C₁-C₁₀ alkyl,C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl, OR⁷, aryloxy, aryl, e.g. phenyl orbenzyl, heteroaryl, heterocyclyl group, and groups of formula Ib shownbelow, wherein each of said alkyl, cycloalkyl, aryl, heteroaryl,heterocyclyl and groups of formula Ib is optionally substituted with oneto four R^(a) groups;

wherein,p is 0 or 1;l is 1, 2 or 3;X³ is, independently at each occurrence, selected from CH or N;X⁴ is selected from C═O, CR^(b)R^(c), O, S, or NR⁷;R^(e), if denoted in formula Ib, may also occur twice as substituent atthe same carbon atom wherein R^(e) is independently selected at eachoccurrence;R^(a) is independently, at each occurrence, selected from the groupconsisting of hydrogen, halogen, C₁-C₃ alkyl, C₁-C₄ alkoxy, alkoxysubstituted with aryl, e.g. phenyl or benzyl, aryloxy; C₁-C₃ haloalkyl,hydroxyl, C₁-C₃ alkylhydroxyl, —CN, NO₂, —NR^(b)R^(c), —C(O)NR^(b)R^(c),—OR^(c), —C(O)R^(c), —C(O)OR^(c), sulfonyl, sulfoxide, C₃-C₁₀cycloalkyl, heterocyclyl, heteroaryl and aryl, e.g. phenyl, benzyl,alkylaryl wherein each of said alkyl, cycloalkyl, aryl, heteroaryl andheterocyclyl is optionally substituted with one to four C₁-C₃ alkyl,C₁-C₄ alkoxy, aryl, e.g. phenyl or benzyl, halogen, C₁-C₃ haloalkyl,hydroxyl, —NH₂, wherein such substitution, if present, may occur in sucha manner that there is more than one substituent, e.g. two or threesubstituents, per carbon atom, wherein such two or three substituentsmay be the same or different;R^(b) and R^(c) are independently, at each occurrence, selected from thegroup consisting of hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃haloalkyl, C₁-C₆ alkyl-O-alkyl, C₂-C₁₀ alkenyl, C₁-C₄ alkoxy, C₁-C₃alkylhydroxyl, C₃-C₁₀ cycloalkenyl, C₂-C₁₀ alkynyl, haloalkyl, aryl,e.g. phenyl, benzyl, alkylaryl, heteroaryl, and heterocyclyl, whereineach of said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl isoptionally substituted with one to four C₁-C₃ alkyl, C₁-C₄ alkoxy, e.g.methoxy, halogen, aryloxy, C₁-C₃ haloalkyl, e.g. trifluoromethyl,hydroxyl, C₁-C₃ alkylhydroxyl, —CN, —NO₂, —NH₂, sulfonyl, sulfoxide,C₃-C₁₀ cycloalkyl, heterocyclyl, aryl, e.g. phenyl, benzyl, heteroaryl,wherein such substitution, if present, may occur in such a manner thatthere is more than one substituent, e.g. two or three substituents, percarbon atom, wherein such two or three substituents may be the same ordifferent; orR^(b) and R^(c) are connected to each other to make a four, five or sixmembered saturated or unsaturated cyclic or heterocyclic ring, or theyare connected to make a fused cyclic or heterocyclic ring structure;R^(d) is independently, at each occurrence, selected from the groupconsisting of hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl,aryl, e.g. phenyl or benzyl, heteroaryl and heterocyclyl group, whereineach of said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl isoptionally substituted with one to four R^(a) groups;R^(e) is independently, at each occurrence, selected from the groupconsisting of hydrogen, halogen, C₁-C₁₀ alkyl, C₃-C₁₀cyclo alkyl,C₁-C₃haloalkyl, hydroxyl, —CN, —(CH₂)_(l)R⁷ with l being 0, 1, 2 or 3,—NO₂, —NH₂, —NR^(b)R^(c), —N(R⁷)C(O)R⁷, —C(O)R⁷, —C(O)OR⁷,—C(O)NR^(b)R^(c), —S(O)R⁷, —S(O)₂R⁷, —S(O)₂NR^(b)R^(c), aryl, e.g.phenyl or benzyl, heteroaryl and heterocyclyl group, wherein each ofsaid alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionallysubstituted with one to four R^(a) groups;R⁷ is independently, at each occurrence, selected from the groupconsisting of hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃haloalkyl, aryl, e.g. phenyl or benzyl, heteroaryl, and heterocyclyl,wherein each of said alkyl, cycloalkyl, aryl, heteroaryl andheterocyclyl is optionally substituted with one to four R^(a) groups,and pharmaceutically acceptable salts thereof.

In one embodiment, the present invention also relates topharmaceutically acceptable salts of the compounds according to thepresent invention.

The term “alkyl” refers to a monovalent straight or branched chain,saturated aliphatic hydrocarbon radical having a number of carbon atomsin the specified range. Thus, for example, “C₁-C₆ alkyl” refers to anyof the hexyl alkyl and pentyl alkyl isomers as well as n-, iso-, sec-,and t-butyl, n- and isopropyl, ethyl and methyl.

Alkyl groups may be optionally substituted with one or more substituentswith one or more substituents as defined herein. Alkyl groups may bestraight or branched. Representative branched alkyl groups have one,two, or three branches. In one embodiment, “alkyl” refers to C₁, C₂, C₃,C₄, C₅, C₆, C₇, C₈, C₉, C₁₀, C₁₁, C₁₂, C₁₃, C₁₄, C₁₅, C₁₆ C₁₇, C₁₈, C₁₉,C₂₀, C₂₁, C₂₂, C₂₃ and/or C₂₄, alkyl, and combinations of any of theforegoing including the ranges C₁ to C₄, alkyl, C₂-C₄ alkyl, C₂-C₁₂alkyl, C₃-C₆ alkyl, C₃-C₁₂ alkyl, C₄-C₆ alkyl, C₄-C₈ alkyl, C₄-C₁₀alkyl, C₄-C₁₂ alkyl, C₅-C₈ alkyl, C₅-C₁₀ alkyl, C₅-C₁₂ alkyl, C₅-C₁₄alkyl, C₆-C₈ alkyl, C₆-C₁₀ alkyl, C₆-C₁₂ alkyl.

The term “alkoxy” means a group having the formula —O-alkyl, in which analkyl group, as defined above, is attached to the parent molecule via anoxygen atom. The alkyl portion of an alkoxy group can have 1 to 20carbon atoms (i.e., C₁-C₂₀ alkoxy), 1 to 12 carbon atoms (i.e., C₁-C₁₂alkoxy), or 1 to 6 carbon atoms (i.e., C₁-C₆ alkoxy). Examples ofsuitable alkoxy groups include, but are not limited to, methoxy (—O—CH₃or OMe), ethoxy (—OCH₂CH₃ or -OEt), t-butoxy (—O—C(CH₃)₃ or -OtBu) andthe like.

The term “alkenyl” refers to a monovalent straight or branched chainaliphatic hydrocarbon radical containing one or more carbon-carbondouble bonds and having a number of carbon atoms in the specified range.Thus, for example, “C₂-C₆ alkenyl” refers to all of the hexenyl andpentenyl isomers as well as 1-butenyl, 2-butenyl, 3-butenyl, isobutenyl,1-propenyl, 2-propenyl, and ethenyl (or vinyl). Examples of alkenylsuseful in accordance with the present invention are C₂-C₁₀, C₂-C₉,C₂-C₈, C₂-C₇, C₂-C₆, C₂-C₅ and C₂-C₄ alkenyl.

The term “alkynyl” refers to a monovalent straight or branched chainaliphatic hydrocarbon radical containing one carbon-carbon triple bondand having a number of carbon atoms in the specified range. Thus, forexample, “C₂-C₆ alkynyl” refers to all of the hexynyl and pentynylisomers as well as 1-butynyl, 2-butynyl, 3-butynyl, 1-propynyl,2-propynyl, and ethynyl. Examples of alkynyls useful in accordance withthe present invention are C₂-C₁₀, C₂-C₉, C₂-C₈, C₂-C₇, C₂-C₆, C₂-C₅ andC₂-C₄ alkynyl.

The term “alkylene” refers to a saturated, branched or straight chain orcyclic hydrocarbon radical having two monovalent radical centers derivedby the removal of two hydrogen atoms from the same or two differentcarbon atoms, 1 to 10 carbon atoms, or 1 to 6 carbon atoms. Typicalalkylene radicals include, but are not limited to, methylene (—CH₂—),1,1-ethyl (—CH(CH₃)—), 1,2-ethyl (—CH₂CH₂—), 1,1-propyl (—CH(CH₂CH₃)—),1,2-propyl (—CH₂CH(CH₃)—), 1,3-propyl (—CH₂CH₂CH₂—), 1,4-butyl(—CH₂CH₂CH₂CH₂—), and the like.

The term “alkenylene” refers to an unsaturated, branched or straightchain or cyclic hydrocarbon radical having two monovalent radicalcenters derived by the removal of two hydrogen atoms from the same ortwo different carbon atoms of parent alkene. For example, an alkenylenegroup can have 1 to 20 carbon atoms, 1 to 10 carbon atoms, or 1 to 6carbon atoms. Typical alkenylene radicals include, but are not limitedto, 1,2-ethenyl (—CH═CH—).

The term “alkynylene” refers to an unsaturated, branched or straightchain or cyclic hydrocarbon radical having two monovalent radicalcenters derived by the removal of two hydrogen atoms from the same ortwo different carbon atoms of parent alkyne. For example, an alkynylenegroup can have 1 to 20 carbon atoms, 1 to 10 carbon atoms or 1 to 6carbon atoms. Typical alkynylene radicals include, but are not limitedto, acetylene propargyl (—CH₂C≡C—), and 4-pentynyl (—CH₂CH₂CH₂C≡CH—).

The term “cycloalkyl”, alone or in combination with any other term,refers to a group, such as optionally substituted or non-substitutedcyclic hydrocarbon, having from three to eight carbon atoms, unlessotherwise defined. Thus, for example, “C₃-C₈ cycloalkyl” refers tocyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, andcyclooctyl. Cycloalkyl groups may be optionally substituted with one ormore substituents as defined herein. Cycloalkyl includes cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl. Examples ofsubstituents that are suitable include but are not limited to hydroxyl,halogen, cyano, sulfonyl, further aryl(s), C₁-C₅ alkyl, C₁-C₄ alkoxy,oxo, C₃-C₆ cycloalkyl, heteroaryl, heterocycloalkyl, C₁-C₃ sulfanyl.

The term “haloalkyl” refers to an alkyl group, as defined herein that issubstituted with at least one halogen. Examples of straight or branchedchained “haloalkyl” groups useful in the present invention include, butare not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, andt-butyl substituted independently with one or more halogens, e.g. 2, 3,4, 5 or 6 substituent halogens. The term “haloalkyl” should beinterpreted to include such substituents such as —CH₂F, —CHF₂, —CF₃,—CH₂—CH₂—F, —CHF—CH₂F, —CH₂—CF₃, and the like.

The term “heteroalkyl” refers to an alkyl group where one or more carbonatoms have been replaced with a heteroatom, such as, O, N, or S. Forexample, if the carbon atom of alkyl group which is attached to theparent molecule is replaced with a heteroatom (e.g., O, N, or S) theresulting heteroalkyl groups are, respectively, an alkoxy group (e.g.,—OCH₃, etc.), an amine (e.g., —NHCH₃, —N(CH₃)₂, etc.), or thioalkylgroup (e.g., —SCH₃, etc.). If a non-terminal carbon atom of the alkylgroup which is not attached to the parent molecule is replaced with aheteroatom (e.g., O, N, or S) and the resulting heteroalkyl groups are,respectively, an alkyl ether (e.g., —CH₂CH₂—O—CH₃, etc.), alkyl amine(e.g., —CH₂NHCH₃, —CH₂N(CH₃)₂, etc.), or thioalkyl ether (e.g.,—CH₂—S—CH₃).

The term “halogen” refers to fluorine, chlorine, bromine, or iodine.

The term “aryl” refers to (i) optionally substituted phenyl, (ii)optionally substituted benzyl, (iii) optionally substituted 9- or 10membered bicyclic, fused carbocyclic ring systems in which at least onering is aromatic, and (iv) optionally substituted 11- to 14-memberedtricyclic, fused carbocyclic ring systems in which at least one ring isaromatic. Suitable aryls include, for example, phenyl, biphenyl,naphthyl, tetrahydronaphthyl (tetralinyl), indenyl, anthracenyl, andfluorenyl. Aryl groups may be optionally substituted with one or moresubstituents as defined herein. Examples of substituents that aresuitable include but are not limited to hydroxyl, halogen, cyano,sulfonyl, further aryl(s), C₁-C₅ alkyl, C₁-C₄ alkoxy, oxo, C₃-C₆cycloalkyl, heteroaryl, heterocycloalkyl, C₁-C₃ sulfanyl.

The term “benzyl” as used herein is meant to indicate an optionallysubstituted or non-substituted benzyl group.

The term “heteroaryl” refers to (i) optionally substituted 5- and6-membered heteroaromatic rings and (ii) optionally substituted 9- and10-membered bicyclic, fused ring systems in which at least one ring isaromatic, wherein the heteroaromatic ring or the bicyclic, fused ringsystem contains from 1 to 4 heteroatoms independently selected from N,O, and S, where each N is optionally in the form of an oxide and each Sin a ring which is not aromatic is optionally S(O) or S(O)₂. Suitable 5-and 6-membered heteroaromatic rings include, for example, pyridyl,pyrrolyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, thienyl,furanyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl,isooxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, and thiadiazolyl.Suitable 9- and 10-membered heterobicyclic, fused ring systems include,for example, benzofuranyl, indolyl, indazolyl, naphthyridinyl,isobenzofuranyl, benzopiperidinyl, benzisoxazolyl, benzoxazolyl,chromenyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl,tetrahydroquinolinyl, tetrahydroisoquinolinyl, isoindolyl,benzodioxolyl, benzofuranyl, imidazo[1,2-a]pyridinyl, benzotriazolyl,dihydroindolyl, dihydroisoindolyl, indazolyl, indolinyl, isoindolinyl,quinoxalinyl, quinazolinyl, 2,3-dihydrobenzofuranyl, and2,3-dihydrobenzo-1,4-dioxinyl.

The term “heterocyclyl” refers to (i) optionally substituted 4- to8-membered, saturated and unsaturated but non-aromatic monocyclic ringscontaining at least one carbon atom and from 1 to 4 heteroatoms, (ii)optionally substituted bicyclic ring systems containing from 1 to 6heteroatoms, and (iii) optionally substituted tricyclic ring systems,wherein each ring in (ii) or (iii) is independent of fused to, orbridged with the other ring or rings and each ring is saturated orunsaturated but nonaromatic, and wherein each heteroatom in (i), (ii),and (iii) is independently selected from N, O, and S, wherein each N isoptionally in the form of an oxide and each S is optionally oxidized toS(O) or S(O)2. Suitable 4- to 8-membered saturated heterocyclylsinclude, for example, azetidinyl, piperidinyl, morpholinyl,thiomorpholinyl, thiazolidinyl, isothiazolidinyl, oxazolidinyl,isoxazolidinyl, imidazolidinyl, piperazinyl, tetrahydropyranyl,tetrahydrothienyl, pyrazolidinyl, hexahydropyrimidinyl, thiazinanyl,thiazepanyl, azepanyl, diazepanyl, tetrahydropyranyl,tetrahydrothiopyranyl, dioxanyl, and azacyclooctyl. Suitable unsaturatedheterocyclic rings include those corresponding to the saturatedheterocyclic rings listed in the above sentence in which a single bondis replaced with a double bond. It is understood that the specific ringsand ring systems suitable for use in the present invention are notlimited to those listed in this and the preceding paragraphs. Theserings and ring systems are merely representative.

“Optionally substituted” indicates that a group, such as alkyl, alkenyl,alkynyl, aryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocyclylor heteroaryl, may be unsubstituted, or the group may be substitutedwith one or more substituents as defined herein.

“Pharmaceutically acceptable” refers to those compounds, materials,compositions, and dosage forms which are, within the scope of soundmedical judgment, suitable for use in contact with the tissues of humanbeings or animals without excessive toxicity, irritation, or otherproblem or complication, commensurate with a reasonable benefit/riskratio.

“Substituted” in reference to a group indicates that one or morehydrogen atoms attached to a member atom within the group is replacedwith a substituent selected from the group of defined or suitablesubstituents. It should be understood that the term “substituted”includes the implicit provision that such substitution be in accordancewith the permitted valence of the substituted atom and the substituent,and that the substitution results in a stable compound. When it isstated that a group may contain one or more substituents, one or moremember atom within the group may be substituted. In addition, a singlemember atom within the group may be substituted with more than onesubstituent as long as such substitution is in accordance with thepermitted valence of the atom.

The term “MIC₅₀” refers to the concentration of compound which inhibitsbacterial growth, preferably growth of M. tuberculosis, in comparison toa control without any drug after five days by 50%.

In a further aspect, the present invention relates to compounds havingone of the formulae 1-360, as shown in Tables 1-2, preferably 3, 6, 8,13, 14, 17-20, 22, 24, 25, 27-29, 32, 35, 36, 38-58, 60-68, 72, 74-80,82-87, 90-92, 95-97, 99-101, 103-108, 110-112, 114-116, 118-122,124-127, 129, 130, 132-140, 142-146, 149, 151-156, 158-162, 165,167-169, 171, 174, 177, 178, 180, 183, 186, 188, 192-197, 199, 201-204,206-209, 211-229, 231-254, 256, 258-262, 264-268, 271-279, 281-285,287-294, 296-299, 301, 302, 304-309, 311, 313-325, 327-346, 348-355,357-360, more preferably 3, 13, 14, 32, 35, 36, 38-50, 53-55, 58, 61,63, 66-68, 72, 74, 76-80, 83-86, 90, 91, 95, 96, 99-101, 103-108,110-112, 114, 115, 118-122, 124, 125, 127, 129, 130, 132-138, 142-146,151, 153-156, 158-162, 167, 168, 171, 174, 177, 180, 183, 186, 188,193-195, 197, 199, 201-204, 206-209, 211-222, 224-226, 228, 231-252,254, 256, 258-262, 265, 266, 268, 271-278, 282-285, 287-294, 296, 298,299, 301, 302, 304-309, 314-320, 323-325, 328-334, 336-346, 348-352,358-360 as shown in Tables 1-2.

Preferably, the compounds as defined above have an inhibitory activityon bacterial growth, preferably on the growth of M. tuberculosis, insidea host cell, preferably a macrophage, at a concentration between 1-20μM, preferably less than 1 μM.

In one aspect, the present invention relates to compounds as definedabove for use in the treatment of a bacterial infection, e.g.tuberculosis.

In one aspect, the present invention relates to compounds as definedabove for use in the treatment of Tuberculosis.

In one aspect, the present invention relates to a composition,preferably a pharmaceutical composition comprising a compound as definedabove, and a pharmaceutically acceptable carrier.

In one aspect, the present invention relates to a method of treatment ofa bacterial infection, in particular Tuberculosis, comprising theapplication of a suitable amount of a compound as defined above or of apharmaceutical composition as defined above to a person in need thereof.

In one embodiment, a “suitable amount”, as used herein, is meant torefer to an amount in the range of from 0.01 mg/kg body weight to 1 g/kgbody weight.

The objects of the present invention are also solved by a compound thatcompetitively inhibits the specific binding of a compound according tothe present invention. Preferably, such specific binding is with respectto a target protein of said compound according to the present invention.The objects of the invention are also solved by a pharmaceuticalcomposition comprising such competitively inhibiting compound, asdefined above, and a pharmaceutically acceptable carrier.

The objects of the present invention are also solved by a method oftreatment of a bacterial infection, in particular tuberculosiscomprising the application of a suitable amount of a compound whichcompound is characterized by an ability to competitively inhibit thespecific binding of a compound according to the present invention to atarget protein, or the application of a suitable amount of thepharmaceutical composition comprising such competitively inhibitingcompound, to a person in need thereof.

Pharmaceutical Compositions

Pharmaceutically Acceptable Salts

Examples of pharmaceutically acceptable addition salts include, withoutlimitation, the non-toxic inorganic and organic acid addition salts suchas the acetate derived from acetic acid, the aconate derived fromaconitic acid, the ascorbate derived from ascorbic acid, thebenzenesulfonate derived from benzensulfonic acid, the benzoate derivedfrom benzoic acid, the cinnamate derived from cinnamic acid, the citratederived from citric acid, the embonate derived from embonic acid, theenantate derived from enanthic acid, the formate derived from formicacid, the fumarate derived from fumaric acid, the glutamate derived fromglutamic acid, the glycolate derived from glycolic acid, thehydrochloride derived from hydrochloric acid, the hydrobromide derivedfrom hydrobromic acid, the lactate derived from lactic acid, the maleatederived from maleic acid, the malonate derived from malonic acid, themandelate derived from mandelic acid, the methanesulfonate derived frommethane sulphonic acid, the naphthalene-2-sulphonate derived fromnaphtalene-2-sulphonic acid, the nitrate derived from nitric acid, theperchlorate derived from perchloric acid, the phosphate derived fromphosphoric acid, the oxalate derived from oxalic acid, the phthalatederived from phthalic acid, the salicylate derived from salicylic acid,the sorbate derived from sorbic acid, the stearate derived from stearicacid, the succinate derived from succinic acid, the sulphate derivedfrom sulphuric acid, the tartrate derived from tartaric acid, thetoluene-p-sulphonate derived from p-toluene sulphonic acid, and thelike. Such salts may be formed by procedures well known and described inthe art.

Other acids, which may not be considered pharmaceutically acceptable,may be useful in the preparation of salts useful as intermediates inobtaining a chemical compound of the invention and its pharmaceuticallyacceptable acid addition salt.

In another embodiment, the compounds of the invention are used in theirrespective free base form according to the present invention.

Metal salts of a chemical compound of the invention include alkali metalsalts, such as the sodium salt of a chemical compound of the inventioncontaining a carboxy group.

The chemical compounds of the invention may be provided in unsolvated orsolvated forms together with a pharmaceutically acceptable solvent(s)such as water, ethanol, and the like. Solvated forms may also includehydrated forms such as the monohydrate, the dihydrate, the hemihydrate,the trihydrate, the tetrahydrate, and the like. In general, solvatedforms are considered equivalent to unsolvated forms for the purposes ofthis invention.

Administration and Formulation

The production of medicaments containing the compounds of the invention,its active metabolites or isomers and salts according to the inventionand their application can be performed according to well-knownpharmaceutical methods.

While the compounds of the invention, useable according to the inventionfor use in therapy, may be administered in the form of the raw chemicalcompound, it is preferred to introduce the active ingredient, optionallyin the form of a physiologically acceptable salt in a pharmaceuticalcomposition together with one or more adjuvants, excipients, carriers,buffers, diluents, and/or other customary pharmaceutical auxiliaries.Such salts of the compounds of the invention may be anhydrous orsolvated.

In a preferred embodiment, the invention provides medicaments comprisinga compound useable according to the invention, or a pharmaceuticallyacceptable salt or derivative thereof, together with one or morepharmaceutically acceptable carriers therefor, and, optionally, othertherapeutic and/or prophylactic ingredients. The carrier(s) must be“acceptable” in the sense of being compatible with the other ingredientsof the formulation and not harmful to the recipient thereof.

A medicament of the invention may be those suitable for oral, rectal,bronchial, nasal, topical, buccal, sub-lingual, transdermal, vaginal orparenteral (including cutaneous, subcutaneous, intramuscular,intraperitoneal, intravenous, intraarterial, intracerebral, intraocularinjection or infusion) administration, or those in a form suitable foradministration by inhalation or insufflation, including powders andliquid aerosol administration, or by sustained release systems. Suitableexamples of sustained release systems include semipermeable matrices ofsolid hydrophobic polymers containing the compound of the invention,which matrices may be in form of shaped articles, e.g. films ormicrocapsules.

The compounds useable according to the invention, together with aconventional adjuvant, carrier, or diluent, may thus be placed into theform of medicament and unit dosages thereof. Such forms include solids,and in particular tablets, filled capsules, powder and pellet forms, andliquids, in particular aqueous or non-aqueous solutions, suspensions,emulsions, elixirs, and capsules filled with the same, all for oral use,suppositories for rectal administration, and sterile injectablesolutions for parenteral use. Such medicament and unit dosage formsthereof may comprise conventional ingredients in conventionalproportions, with or without additional active compounds or principles,and such unit dosage forms may contain any suitable effective amount ofthe active ingredient commensurate with the intended daily dosage rangeto be employed.

The compounds useable according to the invention can be administered ina wide variety of oral and parenteral dosage forms. It will be obviousto those skilled in the art that the following dosage forms maycomprise, as the active component, either a compound(s) useableaccording to the invention or a pharmaceutically acceptable salt of acompound(s) useable according to the invention.

For preparing a medicament from a compound useable according to theinvention, pharmaceutically acceptable carriers can be either solid orliquid. Solid form preparations include powders, tablets, pills,capsules, cachets, suppositories, and dispersible granules. A solidcarrier can be one or more substances which may also act as diluents,flavouring agents, solubilizers, lubricants, suspending agents, binders,preservatives, tablet disintegrating agents, or an encapsulatingmaterial.

In powders, the carrier is a finely divided solid which is in a mixturewith the finely divided active component. In tablets, the activecomponent is mixed with the carrier having the necessary bindingcapacity in suitable proportions and compacted in the shape and sizedesired. Suitable carriers are magnesium carbonate, magnesium stearate,talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth,methylcellulose, sodium carboxymethylcellulose, a low melting wax, cocoabutter, and the like. The term “preparation” is intended to include theformulation of the active compound with encapsulating material ascarrier providing a capsule in which the active component, with orwithout carriers, is surrounded by a carrier, which is thus inassociation with it. Similarly, cachets and lozenges are included.Tablets, powders, capsules, pills, cachets, and lozenges can be used assolid forms suitable for oral administration.

For preparing suppositories, a low melting wax, such as a mixture offatty acid glyceride or cocoa butter, is first melted and the activecomponent is dispersed homogeneously therein, as by stirring. The moltenhomogenous mixture is then poured into convenient sized moulds, allowedto cool, and thereby to solidify. Compositions suitable for vaginaladministration may be presented as pessaries, tampons, creams, gels,pastes, foams or sprays containing in addition to the active ingredientsuch carriers as are known in the art to be appropriate. Liquidpreparations include solutions, suspensions, and emulsions, for example,water or water-propylene glycol solutions. For example, parenteralinjection liquid preparations can be formulated as solutions in aqueouspolyethylene glycol solution.

The chemical compounds according to the present invention may thus beformulated for parenteral administration (e.g. by injection, for examplebolus injection or continuous infusion) and may be presented in unitdose form in ampoules, pre-filled syringes, small volume infusion or inmulti-dose containers with an added preservative. The compositions maytake such forms as suspensions, solutions, or emulsions in oily oraqueous vehicles, and may contain formulation agents such as suspending,stabilising and/or dispersing agents. Alternatively, the activeingredient may be in powder form, obtained by aseptic isolation ofsterile solid or by lyophilization from solution, for constitution witha suitable vehicle, e.g. sterile, pyrogen-free water, before use.

Aqueous solutions suitable for oral use can be prepared by dissolvingthe active component in water and adding suitable colorants, flavours,stabilising and thickening agents, as desired. Aqueous suspensionssuitable for oral use can be made by dispersing the finely dividedactive component in water with viscous material, such as natural orsynthetic gums, resins, methylcellulose, sodium carboxymethylcellulose,or other well known suspending agents.

Also included are solid form preparations which are intended to beconverted, shortly before use, to liquid form preparations for oraladministration. Such liquid forms include solutions, suspensions, andemulsions. These preparations may contain, in addition to the activecomponent, colorants, flavours, stabilisers, buffers, artificial andnatural sweeteners, dispersants, thickeners, solubilizing agents, andthe like.

In one embodiment of the present invention, the medicament is appliedtopically or systemically or via a combination of the two routes.

For administration, the compounds of the present invention may, in oneembodiment, be administered in a formulation containing 0.001% to 70%per weight of the compound, preferably between 0.01% to 70% per weightof the compound, even more preferred between 0.1% and 70% per weight ofthe compound. In one embodiment, a suitable amount of compoundadministered is in the range of from 0.01 mg/kg body weight to 1 g/kgbody weight.

Compositions suitable for administration also include lozengescomprising the active agent in a flavoured base, usually sucrose andacacia or tragacanth; pastilles comprising the active ingredient in aninert base such as gelatin and glycerol or sucrose and acacia; andmouthwashes comprising the active ingredient in a suitable liquidcarrier.

Solutions or suspensions are applied directly to the nasal cavity byconventional means, for example with a dropper, pipette or spray. Thecompositions may be provided in single or multi-dose form. In the lattercase of a dropper or pipette, this may be achieved by the patientadministering an appropriate, predetermined volume of the solution orsuspension. In the case of a spray, this may be achieved for example bymeans of a metering atomizing spray pump.

Administration to the respiratory tract may also be achieved by means ofan aerosol formulation in which the active ingredient is provided in apressurised pack with a suitable propellant such as a chlorofluorocarbon(CFC) for example dichlorodifluoromethane, trichlorofluoromethane, ordichlorotetrafluoroethane, carbon dioxide, or other suitable gas.

The aerosol may conveniently also contain a surfactant such as lecithin.The dose of drug may be controlled by provision of a metered valve.

Alternatively the active ingredients may be provided in the form of adry powder, for example a powder mix of the compound in a suitablepowder base such as lactose, starch, starch derivatives such ashydroxypropylmethyl cellulose and polyvinylpyrrolidone (PVP).Conveniently the powder carrier will form a gel in the nasal cavity. Thepowder composition may be presented in unit dose form for example incapsules or cartridges of, e.g., gelatin, or blister packs from whichthe powder may be administered by means of an inhaler.

In compositions intended for administration to the respiratory tract,including intranasal compositions, the compound will generally have asmall particle size for example of the order of 5 microns or less. Sucha particle size may be obtained by means known in the art, for exampleby micronization.

When desired, compositions adapted to give sustained release of theactive ingredient may be employed.

The pharmaceutical preparations are preferably in unit dosage forms. Insuch form, the preparation is subdivided into unit doses containingappropriate quantities of the active component. The unit dosage form canbe a packaged preparation, the package containing discrete quantities ofpreparation, such as packaged tablets, capsules, and powders in vials orampoules. Also, the unit dosage form can be a capsule, tablet, cachet,or lozenge itself, or it can be the appropriate number of any of thesein packaged form. Tablets or capsules for oral administration andliquids for intravenous administration and continuous infusion arepreferred compositions.

Further details on techniques for formulation and administration may befound in the latest edition of Remington's Pharmaceutical Sciences(Maack Publishing Co. Easton, Pa.).

Tables

Reference is now made to the tables, wherein

Table 1 summarizes compounds 1-360 in terms of their structures andcorresponding characteristics.Table 2 summarizes the compounds (general scaffolds I-IV) with theirrespective inhibitory activities; the in vitro growth fluorescence assay(QUM) and the intracellular growth assay (QIM).Table 3 shows anti-bacterial activity for compound 83, 127, 144 andcompound 202 on several multi-drug resistant (MDR) strains.

EXAMPLES

The invention is now further described by reference to the followingexamples which are intended to illustrate, not to limit the scope of theinvention.

Example 1: Determination the Minimum Inhibitory Concentration (MIC) orMIC₅₀ of New Chemical Entities Against M. tuberculosis

The intracellular (QIM) assay and in vitro (QUM) assay, wherein theabbreviation “QIM” stands for Quantification of IntracellularMycobacteria and the abbreviation “QUM” stands for Quantification of invitro grown Mycobacteria, along with the Resazurin Microtitre Assay(REMA) were used to determine the MIC₅₀ value.

The QIM assay to determine MIC₅₀ was performed as now described.Briefly, Raw 264.7 cells were infected with H37Rv-GFP in suspension at aMOI 2:1 in RPMI 1640 supplemented with 10% heat-inactivated FCS for 2hours at 37° C. with shaking. After three washes with RPMI-1% FCS (fetalcalf serum) by centrifugation, 45 μl of 15000 infected cells weredispensed into each plate well pre-plated with 5 μl of compounds to betested and controls. Infected cells were incubated for 5 days at 37° C.,5% CO₂. After five days, macrophages were stained with SYTO 60, 5 μM(Invitrogen, 511342) for 1 hour at 37° C. and image acquisition wasperformed on an EVOscreeen-Mark III fully automated platform(PerkinElmer) integrated with an Opera™ (10×-air objective) and locatedin a BSL-3 safety laboratory. Mycobacteria-GFP were detected using a488-nm laser filter and SYTO 60 labelled cells with a 635-nm laserfilter. Two fields were recorded for each plate well and each image wasthen processed using dedicated in-house image analysis software. Theresults are summarized in Table 2.

The QUM assay to determine MIC₅₀ was performed as now described.Briefly, 384 plates (Greiner, #781091) were first prepared with 0.5 μlof compound to be tested dispensed by EVOBird (Evotec) in 10 ul of7H9-10% ADS-0.05% Tween80. M. tuberculosis H37Rv expressing the greenfluorescent protein (H37Rv-GFP) precultured in separate test tubes at37° C. in Middlebrook 7H9 broth (Difco) supplemented with 0.05% Tween 80(Sigma, P8074), 0.02% Glycerol, 10% Albumin-Dextrose Saline (ADS) and 50ug/ml Hygromycine (Invitrogen) for 5 days until the Optical density (OD)reached between 0.4˜0.5. For the assay, the precultured H37Rv-GFPbacteria were then placed into 7H9-10% ADS-0.05% media aftercentrifugation. Forty microliters of H37Rv-GFP bacterial suspensiondiluted to 2×10⁶ CFU/mL (based on GFP fluorescence assessment and areference curve) was then added to the pre-prepared 384 plates resultingin a final volume of 50 μl containing 1% DMSO. Plates were incubated at37° C., 5% CO₂ for 5 days. Mycobacterial growth was determined bymeasuring GFP-fluorescence using a Victor 3 reader (Perkin-Elmer LifeScience). The results are summarized in Table 2.

The REMA using concentrations of compounds, to be tested, from 60 μM to3 nM was performed as now described. Briefly, 66.6 μl of 7H9-10%ADS-0.05% Tween80 medium was prepared through 3-fold serial dilutions ofdrugs in every well of 96-well microtitre plates except peripheral wellswhere 200 μl sterilized water was added to prevent evaporation duringincubation. 33.3 μl of the Mycobacterium multi-drug resistant (MDR)strains (MDR-33, 137 and 146 are clinical isolates) were added topre-prepared plates resulting in a final volume of 100 μl (finalbacterial OD=0.005) Plates were sealed and incubated at 37° C. for 1week. Twenty-five microliters of 0.02% resazurin (Sigma Chem. Co.)solution was added to each well; plates were re-incubated for anadditional 1 day. A change in color from blue to pink indicated thegrowth of bacteria, and the MIC was read as the minimum compoundconcentration that prevented the color change in resazurin solution. Theresults are summarized in Table 3.

Example 2: Derivatization of the General Scaffolds

The compounds (scaffolds I-IV, see Table 1) underwent derivatizationaccording to the methods outlined below (Schemes 1-31). Resultingderivatives were examined for inhibitory activity (MIC) using the assaysdescribed above (Example 1) and the results are summarized in Tables2-3. The synthesized compounds 1-360 are shown in Table 1.

General Procedure for the Synthesis of A1

To a stirred solution of 2,4-dichlorothiazole-5-carbaldehyde (2.19 mmol)in MeCN (10 mL) were added adequate amine (2.64 mmol) and triethylamine(11.0 mmol) and the mixture was stirred for 2 hours at room temperature.After the reaction completion, the reaction mixture was poured to thecold water and then a resulting solid was collected. The crude compoundwas used for next reaction without further purification or was purifiedby column chromatography as necessary to give A1.

General Procedure for the Synthesis of A2

A mixture of A1 (1.61 mmol), ethylthioglycolate (1.93 mmol) andtriethylamine (3.22 mmol) in DMSO (3.0 mL) was heated to 100° C. for 3hours. The reaction mixture was diluted with EtOAc (15 mL), washed withwater (10 mL), dried over MgSO₄ and concentrated. The resulting residuewas dissolved in EtOH (5.0 mL) and sodium ethoxide solution (21% inEtOH, 2.42 mmol) was added. The reaction mixture was stirred for an hourat room temperature. After the reaction completion, the reaction wasquenched with water (2.0 mL) and the organic solvent was evaporated. Thegenerated precipitates was filtered, washed with water and dried invacuo to give A2.

General Procedure for the Synthesis of A3

To a stirred suspension of A2 (1.26 mmol) in MeOH (6.0 mL) was added anaqueous solution of lithium hydroxide (6.32 mmol in 2.0 mL of water) andthe mixture was heated to 50° C. for 3 hours. The organic solvent wasevaporated and 1N HCl was added until pH was reached to 4. The residualwhite solid was collected by filtration, washed with water and dried invacuo to give A3 as a white solid.

General Procedure for the Synthesis of A5

Method 1:

To a stirred solution of A3 (0.16 mmol) in anhydrous DMF or methylenechloride (2.0 mL) were added1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.24 mmol),1-hydroxybenzotriazole (0.082 mmol), triethylamine (0.33 mmol) andadequate amine A4 (0.15 mmol) at room temperature, then the resultingsolution was stirred for 4 hours at room temperature. The reactionmixture was concentrated and the resulting crude residue was purified byflash column chromatography to give A5.

Method 2:

To a stirred suspension of A3 (1.0 mmol) in methylene chloride (10.0 mL)were added oxalyl chloride (0.50 mL) and 2-drops of N,N-dimethylformamide at room temperature and the reaction mixture wasstirred for 2 hours. After reaction completion, the mixture wasconcentrated and the resulting residue was washed with diethyl ether (20mL×3) and dried to give a acyl chloride. The resulting acyl chloride(0.15 mmol) was dissolved in methylene chloride (3.0 mL) and then A4(0.15 mmol) and triethylamine (0.45 mmol) were added to the solution.The resulting mixture was stirred at room temperature for 3 hours. Afterreaction completion, the mixture was diluted with methylene chloride (10mL), washed with brine (10 mL), dried over MgSO₄ and concentrated invacuo. The crude residue was purified by flash column chromatography togive A5.

Method 3 (from A2):

To a stirred solution of A2 (0.15 mmol) and A4 (0.15 mmol) in toluene(2.0 mL) was added trimethyl aluminum (2.0 M in hexane, 0.23 mmol) underice bath. The resulting mixture was allowed room temperature and thenheated to 80-100° C. After reaction completion, the reaction mixture wascooled to room temperature, quenched with water and then resultingaluminum slurry was filtered off using cellite. The filtrate wasextracted with methylene chloride several times, washed with water andbrine and organic layer was dried over MgSO₄. The crude residue waspurified by flash column chromatography to give A5.

General Procedure for the Synthesis of A6

To a stirred solution of A5 (0.021 mmol) in N,N-dimethylformamide (0.5mL) was added sodium hydride (0.025 mmol) at 0° C. After 20 min ofpre-stirring, iodomethane (0.042 mmol) was added to the solution and themixture was further stirred at room temperature for 2 hours. Afterreaction completion, the reaction mixture was poured to the water (5 mL)and extracted with methylene chloride (10 mL×3). The organic layer waswashed with brine (5 mL), dried over anhydrous Na₂SO₄ and concentratedin vacuo. The resulting crude residue was purified by flash columnchromatography to give A6.

General Procedure for the Synthesis of B1

To a stirred suspension of (2,5-dibromothiazol-4-yl)methanol (0.80 g,2.93 mmol) and NaHCO₃ (1.23 g, 14.65 mmol) in methylene chloride (15.0mL) was added dess-martin periodinane (1.86 g, 4.39 mmol) and thereaction mixture was stirred for 20 min at room temperature. Thereaction mixture was diluted with methylene chloride (10 mL), washedwith water (10 mL), dried over MgSO₄ and concentrated. The crude residuewas purified by flash column chromatography (n-hexane:EtOAc=15:1 to10:1) to give B1 as a white solid (0.71 g, 90%). ¹H NMR (400 MHz,acetone-d₆) δ 9.91 (s, 1H).

General Procedure for the Synthesis of B2

A mixture of B1 (0.64 g, 2.38 mmol) and piperidine (1.5 mL) was heatedto 65° C. for an hour. The reaction mixture was concentrate and theresulting residue was purified by flash column chromatography(n-hexane:EtOAc=15:1 to 10:1) to give B2 as a dark yellow oil (0.49 g,75%). ¹H NMR (400 MHz, acetone-d₆) δ 9.78 (s, 1H), 3.48-3.50 (m, 4H),1.65-1.68 (m, 6H).

General Procedure for the Synthesis of B3

To a stirred solution of B2 (0.49 g, 1.78 mmol) in DMSO (5.0 mL) wereadded ethyl thioglycolate (0.58 uL, 5.34 mmol) and triethyl amine (0.75uL, 5.34 mmol) and then the resulting mixture was heated to 110° C. for3 hours. The reaction mixture was cooled to room temperature, dilutedwith methylene chloride (15 mL). The organic solution was washed withwater (10 mL), dried over MgSO₄ and concentrated. The crude residue waspurified by flash column chromatography (n-hexane:EtOAc=15:1 to 10:1) togive B3 as a red solid (0.34 g, 65%). ¹H NMR (400 MHz, acetone-d₆) δ7.69 (s, 1H), 4.31 (q, J=7.2 Hz, 2H), 3.54-3.56 (m, 4H), 1.67-1.69 (m,6H), 1.34 (t, J=7.2 Hz, 3H).

General Procedure for the Synthesis of C1

A mixture of fuming nitric acid (0.5 mL) and H₂SO₄ (0.4 mL) was addedslowly to a solution of 4-bromothiophene-3-carboxylic acid (1.0 g, 4.83mmol) in H₂SO₄ (2.0 mL) at −10° C. and the resulting mixture was stirredfor 10 min. The reaction mixture was poured to the ice and stirred for 5min. The resulting precipitates was filtered, washed with water anddried in vacuo to give a target compound C1 as a pale yellow solid (1.13g, 93%). ¹H NMR (400 MHz, CDCl₃) δ 8.67 (s, 1H).

General Procedure for the Synthesis of C2

To a solution of C1 (1.10 g, 4.36 mmol) in MeOH (20.0 mL) was addedthionyl chloride (1.6 mL, 22.0 mmol) slowly under ice bath. After theaddition, the ice-bath was removed and the reaction was allowed to warmup to room temperature and further stirred for overnight. The reactionmixture was concentrated and then dissolved in methylene chloride (20mL) The organic solution was washed with aqueous Na₂CO₃ (sat. 20 mL) andbrine (20 mL), dried over MgSO₄ and concentrated in vacuo. The resultingcrude residue was purified by flash column chromatography(n-hexane:EtOAc=5:1 to methylene chloride:EtOAc=5:1) to give C2 as apale yellow solid (0.93 g, 80%). ¹H NMR (400 MHz, CDCl₃) δ 8.29 (s, 1H),3.94 (s, 3H).

General Procedure for the Synthesis of C3

A mixture of C2 (0.50 g, 1.88 mmol) and dried NaSCN (0.46 g, 5.63 mmol)in DMSO (4.0 mL) was heated to 60° C. for 1.5 h. The reaction mixturewas cooled to room temperature, poured to cold water and then theresulting precipitates was filtered and dried in vacuo to give a targetcompound C3 as a pale yellow solid (0.44 g, 96%).

General Procedure for the Synthesis of C4

To a stirred solution of C3 (0.39 g, 1.60 mmol) in AcOH (5.0 mL) wasadded a small portion of Fe. The resulting mixture was stirred forovernight at room temperature. After the reaction completion, thesolution was basified with sat. Na₂CO₃ (aq. 20 mL) and then extractedwith EtOAc (15 mL) several times. The combined organic layer was washedwith brine (10 mL), dried over MgSO₄ and concentrated. The resultingcrude residue was purified by flash column chromatography(n-hexane:EtOAc=2:1) to give C4 as a brown solid (0.10 g, 29%). ¹H NMR(400 MHz, DMSO-d₆) δ 7.91 (s, 1H), 7.52 (s, 2H), 3.82 (s, 3H).

General Procedure for the Synthesis of C5

To a stirred suspension of copper (II) chloride (0.075 g, 0.56 mmol) inacetonitrile (3.0 mL) was added isopentyl nitrite (0.094 uL, 0.70 mmol).After 10 min of stirring, a solution of C4 (0.10 g, 0.46 mmol) inacetonitrile (2.0 mL) was added and the resulting mixture was furtherstirred for 30 min at room temperature. The insoluble residue wasfiltered off by cellite and the filtrate was concentrated in vacuo. Thecrude residue was purified by flash column chromatography(n-hexane:EtOAc=10:1) to give C5 as a yellow solid (0.050 g, 46%).

General Procedure for the Synthesis of C6

A mixture of C5 (0.050 g, 0.21 mmol) and piperidine (1.5 mL) was heatedto 80° C. for an hour. The mixture was diluted with methylene chloride(5 mL), washed with water (5 mL) and brine (5 mL), dried MgSO₄ andconcentrated in vacuo. The crude residue was purified by flash columnchromatography (n-hexane:EtOAc=10:1) to give C6 as a pale yellow solid(0.045 g, 74%). ¹H NMR (400 MHz, acetone-d₆) δ 7.85 (s, 1H), 3.87 (s,3H), 3.54-3.57 (m, 4H), 1.67-1.70 (m, 6H).

General Procedure for the Synthesis of C7

To a stirred suspension of C6 (0.045 g, 0.16 mmol) in MeOH (3.0 mL) wasadded an aqueous solution of lithium hydroxide (0.019 g, 0.80 mmol in1.0 mL of water) and the mixture was heated to 50° C. for 3 hours. Theorganic solvent was evaporated and aqueous 1N HCl was added until pH wasreached to 4. The residual white solid was collected by filtration,washed with water and dried in vacuo to give C7 as a white solid (0.039g, 91%).

General Procedure for the Synthesis of C8

To a stirred solution of C7 (0.039 g, 0.14 mmol) in anhydrous DMF (1.5mL) were added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimidehydrochloride (0.042 g, 0.21 mmol), 1-hydroxybenzotriazole (0.0098 mg,0.073 mmol), triethylamine (40 uL, 0.29 mmol) and p-anisidine (0.015 g,0.12 mmol) at room temperature, then the resulting solution was stirredfor 4 hours at room temperature. The reaction mixture was concentratedand the resulting crude residue was purified by flash columnchromatography (n-hexane:EtOAc=3:1 to 2:1) to give C8 as a pale pinksolid (0.039 g, 85%).

General Procedure for the Synthesis of D2

To a stirred solution of D1 (0.050 g, 0.20 mmol) in methylene chloride(2.0 mL) were added diisopropyl axodicarboclate (43 uL, 0.12 mmol),triphenylphospine (0.062 g, 0.24 mmol) and 4-methoxy phenol (0.015 g,0.12 mmol). The reaction mixture was stirred at room temperature forovernight. After reaction completion, the mixture was concentrated andpurified by flash column chromatography (n-hexane:EtOAc=10:1) to give D2as a white solid (0.011 g, 26%).

General Procedure for the Synthesis of E2& E5

To a stirred solution of E1 or E4 (6.49 mmol) in toluene (5.0 mL) wereadded acetic anhydride (32.0 mmol) and p-toluene sulfonic acidmonohydrate (0.65 mmol) and the resulting mixture was heated to 50° C.After an hour, additional p-toluenesulfonic acid monohydrate (7.14 mmol)was added and the reaction mixture was heated to 120° C. for 2 h. Theresulting mixture was cooled to room temperature, poured to cooled waterand then a resulting solid was collected and dried. The crude productwas purified by flash column chromatography to give E2 or E5.

2-Methyl-5-nitrobenzo[d]oxazole

Pale yellow solid; ¹H NMR (400 MHz, CDCl₃) δ 8.54 (d, J=2.4 Hz, 1H),8.26 (dd, J=8.8, 2.4 Hz, 1H), 7.56 (d, J=8.8 Hz, 1H), 2.71 (s, 3H).

2-Methyl-4-nitrobenzo[d]oxazole

Pale yellow solid; ¹H NMR (400 MHz, CDCl₃) δ 8.15 (dd, J=8.0, 0.8 Hz,1H), 7.80 (dd, J=8.4, 0.8 Hz, 1H), 7.44 (dd, J=8.0, 8.4 Hz, 1H), 2.77(s, 3H).

General Procedure for the Synthesis of E6

A mixture of fuming nitric acid (0.50 mL) and sulfuric acid (0.40 mL)were added to a solution of E5 (2.39 mmol) in sulfuric acid (2.0 mL) at−10° C. The resulting mixture was stirred for 30 min at the sametemperature. Once starting material was disappeared, the reactionmixture was poured to the ice with stirring and then the generated whiteprecipitates were filtered and dried invacuo to give a target compoundE6.

6-Chloro-2-methyl-5-nitrobenzo[d]oxazole

White solid; ¹H NMR (400 MHz, acetone-d₆) δ 8.28 (s, 1H), 8.01 (s, 1H),2.05 (s, 3H).

6-Ethyl-2-methyl-5-nitrobenzo[d]oxazole

White solid; ¹H NMR (400 MHz, acetone-d₆); δ 8.16 (s, 1H), 7.71 (s, 1H),2.95 (q, J=7.2 Hz, 2H), 2.66 (s, 3H), 1.28 (t, J=7.2 Hz, 3H).

General Procedure for the Synthesis of E3 & E7

To a stirred solution of E2 or E6 (1.68 mmol) in a mixture of ethylacetate and methanol (3:1 ratio, 5.0 mL) was added palladium onactivated carbon (30 mg) and the resulting solution was stirred under H₂for 2 hours. The palladium was filtered off by cellite and the filtratewas concentrated in vacuo to give E3 or E7.

General Procedure for the Synthesis of F1

A mixture of 2-amino-4-nitrophenol (1.00 g, 6.49 mmol), trimethylorthoformate (3.98 mL, 36.0 mmol) and p-toluenesulfonic acid (62.0 mg,0.32 mmol) was stirred at 95° C. for an hour. The reaction mixture wascooled to room temperature and then the cold water was poured to thereaction mixture (10.0 mL) The generated solid was filtered, washed withwater and dried to give F1 as a brown needle shape solid (0.54 g, 51%).¹H NMR (400 MHz, CDCl₃) δ 8.52 (d, J=2.0 Hz, 1H), 8.33-8.36 (m, 2H),7.91 (d, J=9.2 Hz, 1H).

General Procedure for the Synthesis of F2

Target compound F2 was synthesized according to general procedure forthe synthesis of E3& E7.

General Procedure for the Synthesis of G1

To a stirred solution of 4-nitrobenzoic acid (1.0 g, 5.98 mmol) inanhydrous DMF (10.0 mL) were added acethydrazide (0.53 g, 7.18 mmol),1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (1.72 g, 8.97 mmol),1-hydroxybenzotriazole (0.40 g, 2.99 mmol) and triethylamine (1.70 mL,2.99 mmol) and the reaction mixture was stirred at room temperature forovernight. After the concentration of the reaction mixture, theresulting residue was dissolved in methylene chloride (20 mL) and washedwith water (10 mL). At that time, the pale yellow precipitates weregenerated and it was filtered and dried to give G1 as a pale yellowsolid. ¹H NMR (400 MHz, DMSO-d₆) δ 10.61 (s, 1H), 9.89 (s, 1H), 8.32 (d,J=8.4 Hz, 2H), 8.06 (d, J=8.4 Hz, 2H), 1.91 (s, 3H).

General Procedure for the Synthesis of G2

A mixture of G1 (0.50 g, 2.24 mmol) and POCl₃ (3.0 mL) was heated to110° C. for 1.5 h. After reaction completion, the reaction mixture wasbasified with 3N NaOH (aq.) and then a generated solid was filtered anddried to give G2 (0.44 g, 96%) as a pale yellow solid. ¹H NMR (400 MHz,DMSO-d₆) δ 8.42 (d, J=9.2 Hz, 2H), 8.23 (d, J=9.2 Hz, 2H), 2.62 (s, 3H).

General Procedure for the Synthesis of G3

Target compound G3 was synthesized according to general procedure forthe synthesis of E3& E7.

General Procedure for the Synthesis of H1

To a stirred solution of 4-fluoropyrazole (0.40 g, 4.65 mmol) in THF(15.0 mL) was added NaH (60% dispersion in paraffin, 0.28 g, 6.97 mmol)under ice bath. After 10 min of stirring, p-methoxybenzyl chloride (0.76mL, 5.58 mmol) was added slowly to the reaction mixture. The resultingsolution was allowed to room temperature and stirred for overnight. Thereaction was quenched with water and extracted with EtOAc (20 mL×2). Theorganic phase was washed with brine (15 mL), dried over MgSO₄ andconcentrated in vacuo to give H1. ¹H NMR (400 MHz, acetone-d₆) δ 7.65(d, J=4.8 Hz, 1H), 7.34 (d, J=4.8 Hz, 1H), 7.23-7.26 (m, 2H), 6.88-6.91(m, 2H), 5.18 (s, 2H).

General Procedure for the Synthesis of H2

To a stirred solution of H1 (0.52 g, 2.52 mmol) in THF (10.0 mL) at −78°C. was added a solution of n-BuLi (2.5 M in n-hexane, 1.5 mL, 3.78 mmol)slowly and the mixture was stirred for 15 min while maintaining thetemperature below −60° C. A solution of 1,2-dibromo-tetrachloroethane(0.98 g, 3.02 mmol) in THF (3.0 mL) was added to the reaction mixtureand the resulting solution was continuously stirred for an additional 2hours. The reaction was quenched with water and extracted with EtOAc (20mL×2). The organic phase was washed with brine (10 mL), dried over MgSO₄and concentrated in vacuo. The crude residue was purified by flashcolumn chromatography (n-hexane:EtOAc=15:1) to give H2 as a white solid(0.49 g, 69%). ¹H NMR (400 MHz, acetone-d₆) δ 7.55 (d, J=4.8 Hz, 1H),7.19-7.21 (m, 2H), 6.89-6.91 (m, 2H), 5.28 (s, 2H).

General Procedure for the Synthesis of H3

To a solution of H2 (0.21 g, 0.73 mmol) in dimethoxyethane (3.0 mL) wereadded 4-nitrophenylboronic acid (0.14 g, 0.81 mmol),1,1′-bis(diphenylphosphino)ferrocene)-dichloropalladium(II) (0.027 g,0.037 mmol) and Na₂CO₃ (0.16 g, 1.47 mmol in 1 mL of water) and themixture was stirred at 140° C. After 3 hours, the mixture was cooled toroom temperature, then the mixture was extracted with EtOAc (10 mL),washed with sat. NaHCO₃ (aq. 10 mL) and brine (10 mL) and dried overMgSO₄ and concentrated. The resulting residue was purified by flashcolumn chromatography (n-hexane:EtOAc=4:1) to give 113 as a pale yellowsolid (0.14 g, 58%). ¹H NMR (400 MHz, acetone-d₆) δ 8.35-8.37 (m, 2H),7.72-7.74 (m, 2H), 7.61 (d, J=4.4 Hz, 1H), 6.97-6.99 (m, 2H), 6.80-6.82(m, 2H), 5.37 (s, 2H).

General Procedure for the Synthesis of H4

A mixture of H3 (0.14 g, 0.43 mmol) and trifluoroacetic acid (3.0 mL)was placed in sealed tube and heated to 80° C. with stirring. After 2hours, the mixture was concentrated and then resulting residue wasdissolved in methylene chloride (5 mL), washed with saturated Na₂CO₃(aq. 5.0 mL), dried over MgSO₄ and concentrated to give H4. The cruderesidue was used for next reaction without further purification.

General Procedure for the Synthesis of H5

To a stirred solution of H4 (0.095 g, 0.46 mmol) in THF (5.0 mL) wasadded NaH (60% dispersion in paraffin, 0.028 g, 0.69 mmol) under icebath. After 10 min of stirring, iodomethane (34 uL, 0.55 mmol) was addedslowly to the reaction mixture. The resulting solution was allowed toroom temperature and stirred for overnight. The reaction was quenchedwith water and extracted with EtOAc (5 mL×2). The organic phase waswashed with brine (5 mL), dried over MgSO₄ and concentrated. The cruderesidue was purified by flash column chromatography (n-hexane:EtOAc=5:1)to give H5 as a white solid (0.078 g, 78%). ¹H NMR (400 MHz, acetone-d₆)δ 8.31-8.33 (m, 2H), 8.06-8.09 (m, 2H), 7.83 (d, J=4.8 Hz, 1H), 3.94 (s,3H).

General Procedure for the Synthesis of H6 & H7

Target compounds H6 & H7 were synthesized according to general procedurefor the synthesis of E3&E7.

General Procedure for the Synthesis of 12

A mixture of I1 (0.28 mmol) and trifluoroacetic acid (3.0 mL) was placedin sealed tube and heated to 120° C. for 4 hours with stirring. Afterreaction completion, the reaction mixture was concentrated and dissolvedwith methylene chloride (10.0 mL) again. The organic solution was washedwith saturated Na₂CO₃ (aq. 10.0 mL), dried over MgSO₄ and concentratedin vacuo. The resulting crude residue was purified by flash columnchromatography (methylene chloride:MeOH=99:1) to give I2. ¹H NMR (400MHz, acetone-d₆) δ 9.28 (s, 1H, NH), 7.89 (s, 1H), 7.66 (d, J=8.8 Hz,2H), 7.08 (s, 2H, NH₂), 6.90 (d, J=8.8 Hz, 2H), 3.78 (s, 3H); LCMS(electrospray) m/z 306 (M+H)⁺.

General Procedure for the Synthesis of I3

To a stirred solution of I2 (0.10 mmol) in N,N-dimethylformamide (3.0mL) were added cyclohexanecarboxylic acid (0.10 mmol),1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (0.12mmol), 1-hydroxybenzotriazole (0.03 mmol) and triethylamine (0.20 mmol)at room temperature. The reaction mixture was stirred at 80° C. for 4hours, diluted with EtOAc (20 mL) and washed with brine (20 mL×3). Theorganic layer was dried over anhydrous MgSO₄ and concentrated invacuo.The crude product was purified by flash column chromatography(n-hexane:EtOAc=2:1) to give 13. ¹H NMR (400 MHz, acetone-d₆) δ 9.47 (s,1H, NH), 8.09 (s, 1H), 7.69 (d, J=8.8 Hz, 2H), 6.92 (d, J=8.8 Hz, 2H),3.79 (s, 3H), 2.63-2.68 (m, 1H), 1.96-2.01 (m, 2H), 1.81-1.84 (m, 2H),1.69-1.72 (m, 1H), 1.51-1.60 (m, 2H), 1.26-1.40 (m, 3H); LCMS(electrospray) m/z 416 (M+H)⁺.

General Procedure for the Synthesis of J2

To a stirred solution of J1 (3.4 mmol) in tetrahydrofuran (20 mL) wasadded lithium aluminum hydride (5.1 mmol) at 0° C. and the reactionmixture was stirred for 2 hours while maintaining the temperature below4° C. The reaction mixture was quenched by water with stirring and theinsoluble solid was filtered off. The filtrate was extracted withmethylene chloride (50 mL×2), dried over anhydrous MgSO₄ andconcentrated invacuo. The crude product was purified by flash columnchromatography (n-hexane:EtOAc=3:1) to give J2. ¹H NMR (400 MHz,DMSO-d₆) 7.02 (s, 1H), 5.39 (t, J=5.6 Hz, 1H, OH), 4.56 (d, J=5.6 Hz,2H), 3.42-3.45 (m, 4H), 1.58-1.60 (in, 6H); LCMS (electrospray) m/z 255(M+H)⁺.

General Procedure for the Synthesis of J3

To a stirred solution of J2 (0.87 mmol) in methylene chloride (20.0 mL)was added dess-martin periodinane (0.95 mmol) and the resulting mixturewas stirred at room temperature for an hour. The reaction mixture wasdiluted with methylene chloride (10.0 mL), washed with brine (20 ml×2),dried over anhydrous MgSO₄ and concentrated invacuo. The crude productwas purified by flash column chromatography (n-hexane:EtOAc=5:1) to giveJ3.

General Procedure for the Synthesis of J4

To a stirred solution of J3 (0.20 mmol) in methylene chloride (10.0 ml)were added p-anisidine (0.22 mmol) and sodium triacetoxyborohydride(0.40 mmol) and the resulting mixture was stirred at room temperaturefor overnight. After reaction completion, the mixture was diluted withmethylene chloride (10 mL), washed with brine (10 ml×2), dried overanhydrous MgSO₄ and concentrated invacuo. The crude residue was purifiedby flash column chromatography (n-hexane:EtOAc=4:1) to give J4. ¹H NMR(400 MHz, acetone-d₆) δ 7.07 (s, 1H), 6.72 (d, J=8.8 Hz, 2H), 6.69 (d,J=8.8 Hz, 2H), 5.09 (brs, 1H, NH), 4.47 (d, J=5.6 Hz, 2H), 3.67 (s, 3H),3.48-3.50 (m, 4H), 1.65-1.68 (m, 6H); LCMS (electrospray) ink 360(M+H)⁺.

General Procedure for the Synthesis of K1

To a stirred solution of 2-methylpropanethioamide (5.0 mmol) in ethanol(5.0 mL) were added ethyl 2-bromoacetate (6.0 mmol) and sodium acetate(7.5 mmol) and the reaction mixture was heated to 80° C. for 6 hourswith stirring. The reaction mixture was evaporated, diluted withmethylene chloride (30 mL), washed with brine (30 mL), dried overanhydrous MgSO₄ and concentrated invacuo. The crude product wasrecrystallized by ether to give K1.

General Procedure for the Synthesis of K2

To a stirred solution of K1 (1.0 mmol) in phosphoryl chloride (1.0 mL)was added N,N-dimethylformamide (1.1 mmol) at room temperature. Thereaction mixture was stirred at 115° C. for 10 hours. The mixture waspoured to the ice and stirred for 30 min and extracted with methylenechloride (20 mL), washed with brine (20 mL), dried over anhydrous MgSO₄and concentrated invacuo. The crude product was purified by flash columnchromatography (n-hexane:EtOAc=8:1) to give K2.

General Procedure for the Synthesis of K3

To a stirred solution of K2 (0.90 mmol) in dimethyl sulfoxide (3.0 mL)were added ethyl 2-mercaptoacetate (1.08 mmol) and triethylamine (1.80mmol) and the reaction mixture was stirred at 110° C. for 4 hours. Thereaction mixture was diluted with EtOAc (30 mL) and washed with brine(30 ml×3). The organic layer was dried over anhydrous MgSO₄ andconcentrated invacuo. The crude product was purified by flash columnchromatography (n-hexane:EtOAc=10:1) to give K3. ¹H NMR (400 MHz,acetone-d₆) δ 8.09 (s, 1H), 4.37 (q, J=7.2 Hz, 2H), 3.39-3.47 (m, 1H),1.44 (d, J=6.8 Hz, 6H), 1.37 (t, J=7.2 Hz, 3H); LCMS (electrospray) m/z256 (M+H)⁺.

General Procedure for the Synthesis of L1

To a stirred solution of dimethyl cyanocarbonimidodithioate (5.0 mmol)in N,N-dimethylformamide (10.0 mL) was added sodium sulfide (5.5 mmol)at room temperature. The reaction mixture was stirred at 70° C. for 2hr. To the mixture were added 1-chloropropan-2-one (10.0 mmol) andpotassium carbonate (10.0 mmol) and the resulting mixture was stirred at50° C. for 2 hr. After reaction completion, the reaction mixture wasadded to water (50.0 mL) and the resulting solid was filtered and driedto give L1.

General Procedure for the Synthesis of L2

To a stirred solution of copper (II) bromide (3.44 mmol) in acetonitrile(20.0 mL) was added tert-butyl nitrite (4.30 mmol) at room temperatureand then the resulting solution was heated to 50° C. After an hour, thereaction mixture was cooled to room temperature, L1 (2.87 mmol) wasadded to the solution and the resulting mixture was further stirred for2 hours. After reaction completion, the mixture was diluted withmethylene chloride (50.0 mL) and washed with brine (30 mL×2). Theorganic layer was dried over anhydrous MgSO₄ and concentrated invacuo.The crude product was purified by flash column chromatography(n-hexane:EtOAc=10:1) to give L2.

General Procedure for the Synthesis of L3

To a stirred solution of L2 (2.42 mmol) in dimethyl sulfoxide (5.0 mL)were added ethyl 2-mercaptoacetate (2.66 mmol) and triethylamine (4.84mmol) at room temperature and the reaction mixture was stirred at 100°C. for 2 hr. The reaction mixture was diluted with EtOAc (30 mL) and theorganic solution was washed with brine (30 mL×2), dried over anhydrousMgSO₄ and concentrated in vacuo. The crude residue was dissolved inethanol (10.0 mL) and sodium ethoxide (21% in EtOH, 4.84 mmol) was addedto the solution at 0° C. The reaction mixture was stirred at 50° C. for1 hr. After reaction completion, the reaction mixture was diluted withmethylene chloride (50 mL) and the organic solution was washed withbrine (50 m), dried over anhydrous MgSO₄ and concentrated in vacuo. Thecrude residue was purified by flash column chromatography(n-hexane:EtOAc=5:1) to give L3.

General Procedure for the Synthesis of L4

A mixture of L3 (1.76 mmol) and morpholine (5.0 mL) was heated to 140°C. for 6 hours with stirring. After reaction completion, the mixture wasdiluted with EtOAc (30.0 mL) and washed with brine (30 mL×2). Theorganic layer was dried over anhydrous MgSO₄ and concentrated invacuo.The crude product was purified by flash column chromatography(n-hexane:EtOAc=2:1) to give L4.

General Procedure for the Synthesis of M1

To a stirred solution of 2,4-dichlorothiazole-5-carbaldehyde (0.50 g,2.75 mmol) and ethane-1,2-diol (0.51 g, 8.24 mmol) in toluene (2.5 mL)was added p-toluenesulfonic acid monohydrate (0.042 g, 0.22 mmol) atroom temperature. The mixture was stirred at 90 r for overnight. Afterreaction completion, the reaction mixture was poured to the water (20mL) and extracted by ethyl acetate (30 mL×3). The organic layer wasdried over anhydrous Na₂SO₄ and concentrated in vacuo. The resultingcrude residue was purified by flash column chromatography(n-hexane:EtOAc=30:1) to give M1.

General Procedure for the Synthesis of M2

To a stirred solution of M1 (0.60 g, 2.65 mmol) in tetrahydrofuran (13.0mL) was added n-butyllithium (2.5M in n-hexane, 2.1 mL, 5.30 mmol) at−78° C. and the reaction mixture was stirred for 2 hours whilemaintaining temperature below −60° C. After reaction completion, thereaction was quenched with water (10 mL) and extracted with ethylacetate (30 mL×3). The organic layer was washed with brine (30 mL),dried over anhydrous Na₂SO₄ and concentrated in vacuo to give M2.

General Procedure for the Synthesis of M3

To a stirred solution of M2 (0.53 g, 2.74 mmol) in tetrahydrofuran (6.0mL) was added 6 N HCl (1.2 in) and the mixture was stirred at roomtemperature for 3 h. The reaction mixture was diluted with water (10 mL)and extracted with ethyl acetate (30 mL×3). The organic layer was driedover anhydrous Na₂SO₄ and concentrated in vacuo to give M3.

General Procedure for the Synthesis of N1

A mixture of 1-fluoro-4-nitrobenzene (2.0 mmol), adequate amine (2.0mmol) and K₂CO₃ (6.0 mmol) in DMSO (5 mL) was heated to 120° C. for 4hours. After the cooling, the mixture was poured to the water and thengenerating solid was filtered, washed with water and dried to give N1.

General Procedure for the Synthesis of O1

To a stirred solution of alcohol as starting material (2.55 mmol),adequate phenol (2.13 mmol) and triphenylphosphane (2.55 mmol) inN,N-dimethylformamide or methylene chloride (7.0 mL) was addeddiisopropyl azodicarboxylate (2.55 mmol) at 0° C. The mixture wasallowed to room temperature and stirred for overnight. After reactioncompletion, the reaction mixture was concentrated in vacuo and then theresulting crude residue was purified by flash column chromatography(n-hexane:EtOAc=20:1) to give O1.

General Procedure for the Synthesis of O2

To a stirred solution of O1 (1.88 mmol) in methylene chloride (4.0 mL)was added trifluoroacetic acid (2.0 ml) at room temperature. The mixturewas stirred at room temperature for an hour. The reaction mixture wasquenched by Sat. Na₂CO₃ aqueous solution (4.0 ml) and extracted bymethylene chloride (20 mL×3). The organic layer was dried over anhydrousNa₂SO₄ and concentrated in vacuo to give O2.

General Procedure for the Synthesis of P1

To a stirred solution of potassium tert-butoxide (2.30 g, 20.30 mmol) intert-butyl alcohol (15 mL) were added phenylhydrazine (1.0 g, 9.25 mmol)and (E)-3-methoxyacrylonitrile (0.77 g, 9.25 mmol) at room temperature.The mixture was stirred at room temperature for overnight. Afterreaction completion, the reaction mixture was added to H₂O (15 mL) andextracted by methylene chloride (45 mL×3). The organic layer was driedover anhydrous Na₂SO₄ and concentrated in vacuo. The resulting cruderesidue was purified by silica gel flash column chromatography(n-hexane:EtOAc=5:1) to give P1.

General Procedure for the Synthesis of Q1

To a stirred solution of methyl morpholine-3-carboxylate (0.050 g, 0.34mmol) in tetrahydrofuran (2.0 mL) were added triethylamine (0.042 g,0.41 mmol) and di-tert-butyl dicarbonate (0.075 g, 0.34 mmol) at roomtemperature. The mixture was stirred at room temperature for overnight.The reaction mixture was added to H₂O (5 mL) and extracted by methylenechloride (15 mL×3). The organic layer was dried over anhydrous Na₂SO₄and concentrated in vacuo. The resulting crude residue was purified byflash column chromatography (n-hexane:EtOAc=10:1) to give Q1.

General Procedure for the Synthesis of Q2 To a stirred solution of Q1(0.090 g, 0.37 mmol) in methanol (1.5 mL) was added sodium hydroxide(0.044 g, 1.10 mmol) in water (0.5 mL) at room temperature. The mixturewas stirred at 75° C. for 3 h. After reaction completion, the reactionmixture was acidified with 6 N HCl aqueous solution until pH 4. Thewhite precipitate was filtered and concentrated in vacuo to give Q2.

General Procedure for the Synthesis of Q3

To a stirred solution of Q2 (0.079 g, 0.34 mmol) in methylene chloride(1.7 mL) were added dimethylamine hydrochloride (0.030 g, 0.37 mmol),1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (0.078 g, 0.41 mmol) and4-dimethylamino pyridine (0.042 g, 0.34 mmol) and triethylamine (0.10 g,1.02 mmol) at room temperature. The mixture was stirred at roomtemperature for overnight. The reaction mixture was diluted withmethylene chloride (10 mL) and washed with water (5 mL). The organiclayer was dried over anhydrous Na₂SO₄ and concentrated in vacuo. Theresulting crude residue was purified by flash column chromatography(n-hexane:EtOAc=10:1) to give Q3.

General Procedure for the Synthesis of Q4

To a stirred solution of Q3 (0.60 g, 2.3 mmol) in methylene chloride(3.0 mL) was added trifluoroacetic acid (1.5 mL) at room temperature.The mixture was stirred at room temperature for 4 hr. The reactionmixture was quenched by sat. Na₂CO₃ aqueous solution (5 mL) andextracted by methylene chloride (15 mL×3). The organic layer was driedover anhydrous Na₂SO₄ and concentrated in vacuo to give Q4.

General Procedure for the Synthesis of R1

To a stirred solution of2-(4-(4-chlorobenzoyl)piperidin-1-yl)-N-(2-methylbenzo[d]oxazol-5-yl)thieno[2,3-d]thiazole-5-carboxamide(0.010 g, 0.019 mmol) in methanol (0.1 mL) was added sodium borohydride(0.0010 g, 0.022 mmol) at room temperature. The mixture was stirred atroom temperature for overnight. After reaction was completed, thereaction mixture was added to H₂O (5 ml) and concentrated in vacuo. Theresulting crude residue was purified by silica gel flash columnchromatography (n-hexane:EtOAc=1:1) to give R1.

General Procedure for the Synthesis of S1

To a solution of 4-methoxybenzaldehyde (0.30 g, 2.21 mmol) andtert-butyl piperazine-1-carboxylate (0.49 g, 2.64 mmol) indichloromethane (8.0 mL) was added NaBH(OAc)₃ (0.93 g, 4.41 mmol). Theresulting mixture was stirred at room temperature for overnight. Afterreaction completion, the reaction mixture was diluted with methylenechloride (30 mL) and washed with water (20 mL) The organic layer wasdried over MgSO₄ and concentrated invacuo. The resulting crude residuewas purified by flash column chromatography (n-hexane:EtOAc=2:1) to giveS1.

General Procedure for the Synthesis of T1

To a stirred solution of 4-nitrobenzamide (0.50 g, 2.69 mmol) inmethylene chloride (15.0 mL) were added triethylamine (0.545 g, 4.04mmol) and propargylamine (0.107 g, 3.23 mmol) at 0° C. The mixture wasallowed to room temperature and stirred for overnight. The reactionmixture was diluted with methylene chloride (15 mL) and washed withwater (20 mL). The organic layer was dried over MgSO₄ and concentratedin vacuo. The resulting crude residue was purified by flash columnchromatography (n-hexane:EtOAc=1:1) to give T1.

General Procedure for the Synthesis of T2

To a stirred solution of T1 (0.142 g, 0.69 mmol) in ethanol (2.8 mL) wasadded a solution of potassium hydroxide (0.078 g, 1.39 mmol) in ethanol(1.9 mL) at room temperature and then the mixture was heated to 50° C.and stirred for overnight. After reaction completion, the reactionmixture was concentrated. The resulting residue was dissolved withmethylene chloride (30 mL) and washed with water (20 mL) and brine (20mL). The organic layer was dried over MgSO₄ and concentrated in vacuoand the resulting crude residue was purified by flash columnchromatography (n-hexane:EtOAc=5:1) to give T2.

General Procedure for the Synthesis of U1

To a stirred solution of ethyl 2-mercaptoacetate (0.82 g, 6.80 mol) inN,N-dimethylformamide (8.5 mL) were added triethylamine (1.5 mL, 10.0mmol) and dimethyl cyanocarbonimidodithioate (1.0 g, 6.80 mol) and themixture was stirred at 100° C. for 2 h. The reaction mixture was cooledto room temperature, diluted with EtOAc (30 mL) and washed with water(30 mL) The organic layer was dried over MgSO₄ and concentrated invacuoand the resulting crude residue was purified by flash columnchromatography (n-hexane:EtOAc=20:1) to give U1. ¹H NMR (400 MHz,acetone-d₆) δ 6.56 (bis, 2H), 4.19 (q, J=7.2 Hz, 2H), 2.67 (s, 3H), 1.27(t, J=7.2 Hz, 3H).

General Procedure for the Synthesis of U2

To a stirred solution of isopentyl nitrite (3.1 mL, 0.023 mmol) inacetonitrile (36.0 mL) was added CuBr₂ (5.1 g, 0.023 mol) at roomtemperature and the resulting solution was heated to 50° C. After anhour, the solution was cooled to room temperature and U1 (2.0 g, 9.0mol) was added slowly. The reaction mixture was further stirred at roomtemperature for overnight. After reaction completion, the solution wasdiluted with water (50 mL) and extracted by EtOAc (30 mL×2). The organiclayer was dried over MgSO₄ and concentrated invacuo. The resulting cruderesidue was purified by flash column chromatography(n-hexane:EtOAc=10:1) to give U2.

General Procedure for the Synthesis of U3

To a stirred solution of U2 (0.89 g, 3.16 mmol) in ethanol (12.0 mL)were added ethyl 2-mercaptoacetate (0.57 mg, 4.75 mmol) and NaOEt (1.8mL, 4.75 mmol) and the resulting mixture was stirred at room temperaturefor overnight. The reaction mixture was diluted with water (20 mL) andextracted by EtOAc (30 mL×2). The organic layer was dried over MgSO₄ andconcentrated in vacuo. The resulting crude residue was purified by flashcolumn chromatography (n-hexane:EtOAc=20:1) to give U3.

General Procedure for the Synthesis of U4

To a stirred solution of U3 (1.11 g, 3.40 mol) in ethanol (13.7 mL) wasadded NaOEt (2.5 mL, 6.90 mol) at room temperature and the mixture wasstirred at 50° C. for an hour. After reaction completion, the reactionmixture was quenched with water (50 mL) and extracted by EtOAc (30mL×2). The organic layer was dried over MgSO₄ and concentrated in vacuo.The resulting crude residue was purified by flash column chromatography(n-hexane:EtOAc=20:1) to give U4.

General Procedure for the Synthesis of U5

To a stirred solution of U4 (0.050 mg, 0.18 mmol) in N,N-dimethylformamide (0.75 mL) were added potassium carbonate (0.038 mg,0.27 mmol) and benzyl bromide (0.032 mg, 0.19 mmol) at room temperatureand the resulting mixture was stirred for overnight. The reactionmixture was diluted with water (10 mL) and extracted by EtOAc (10 mL×2).The organic layer was dried over MgSO₄ and concentrated in vacuo. Theresulting crude residue was purified by flash column chromatography(n-hexane:EtOAc=20:1) to give U5. ¹H NMR (400 MHz, DMSO-d₆) δ 7.46-7.48(m, 2H), 7.32-7.40 (m, 3H), 5.44 (s, 2H), 4.24 (q, J=7.2 Hz, 2H), 2.77(s, 3H), 1.26 (t, J=7.2 Hz, 3H).

General Procedure for the Synthesis of U6

A mixture of U5 (0.26 g, 0.73 mmol) and morpholine (1.5 mL) was heatedto 130° C. with stirring for 3 h. The reaction mixture was diluted withwater (20 mL) and extracted with EtOAc (20 mL×2). The organic layer wasdried over MgSO₄ and concentrated in vacuo. The resulting crude residuewas purified by flash column chromatography (n-hexane:EtOAc=10:1) togive U6. ¹H NMR (400 MHz, DMSO-d₆) δ 7.45-7.47 (m, 2H), 7.30-7.39 (m,3H), 5.37 (s, 2H), 4.18 (q, J=6.8 Hz, 2H), 3.69-3.71 (m, 4H), 3.48-3.53(m, 4H), 1.21 (t, J=6.8 Hz, 3H).

General Procedure for the Synthesis of V1

To a stirred solution of methyl quinoline-6-carboxylate (5.34 mmol) inmethylene chloride (20 mL) was added 3-chloroperbenzoic acid (13.35mmol). The reaction mixture was stirred at room temperature forovernight. After reaction completion, the reaction mixture was dilutedmethylene chloride (5 mL) and washed with brine (5 mL). The organiclayer was dried over anhydrous MgSO₄ and concentrated in vacuo. Thecrude product was purified by flash column chromatography (5% MeOH inmethylene chloride) to give V1.

General Procedure for the Synthesis of V2

To a stirred solution of 6-(methoxycarbonyl) quinoline 1-oxide (0.98mmol) in dichloroethane (3 mL) was added phosphorus(V) oxychloride (3mL) at 0° C. The reaction mixture was stirred at reflux temperature foran hour. The reaction mixture was poured into the ice water andextracted by methylene chloride (10 mL) twice. The organic layer wasdried over anhydrous MgSO₄ and concentrated in vacuo. The crude productwas purified by flash column chromatography (n-hexane:EtOAc=6:1) to giveV2. ¹H NMR (400 MHz, CDCl₃) δ 8.58 (d, J=2.0 Hz, 1H), 8.33 (dd, J=8.82.0 Hz, 1H), 8.21 (d, J=8.8 Hz, 1H), 8.07 (d, J=8.8 Hz, 1H), 7.46 (d,J=8.8 Hz, 1H), 4.00 (s, 3H).

General Procedure for the Synthesis of W1

To a stirred solution ofN-(4-methoxyphenyl)-2-(piperidin-1-yl)thieno[3,2-d]thiazole-5-carboxamide(0.24 mmol) in methylene chloride (3 mL) was added borontribromide (1.0M in methylene chloride, 4 mL) at 0° C. The reaction mixture was stirredat room temperature for 2 hours. After reaction completion, the reactionmixture was quenched with cold water (5 mL) and extracted with methylenechloride (10 mL×2). The organic layer was dried over anhydrous MgSO₄ andconcentrated in vacuo. The crude product was purified by flash columnchromatography (2% MeOH in methylene chloride) to give W1.

General Procedure for the Synthesis of X1

To a stirred solution of 2-(piperidin-1-yl)thieno[2,3-d]thiazole-5-carboxylic acid (1.11 mmol) in tert-buthanol (8mL) was added diphenylphosphorylazide (1.34 mmol). The reaction mixturewas stirred at 95° C. for 4 hours. The reaction mixture was dilutedmethylene chloride (5 mL) and washed with brine (5 mL) The organic layerwas dried over anhydrous MgSO₄ and concentrated in vacuo. The crudeproduct was purified by flash column chromatography(n-hexane:EtOAc=10:1) to give X1.

General Procedure for the Synthesis of X2

To a stirred solution of X1 (0.58 mmol) in 1,4-dioxane (4 mL) was added35% hydrogenchloride (0.7 mL). The reaction mixture was stirred at roomtemperature. After 2 hours, the reaction mixture was concentrated invacuo and the crude product was used for next reaction without furtherpurification to give X2.

General Procedure for the Synthesis of Y1

To a stirred solution of ethyl2-morpholino-3a,6a-dihydrothieno[2,3-d]thiazole-5-carboxylate (0.67mmol) in trifluoroacetic acid/sulfuric acid (2:1 v/v, 3.0 mL) was addedN-bromosuccinimide (1.34 mmol) at 0° C. The reaction mixture was stirredat room temperature for 2 days. The reaction mixture was poured into theice water and extracted with methylene chloride (10 mL×2). The organiclayer was dried over anhydrous MgSO₄ and concentrated in vacuo. Thecrude product was purified by flash column chromatography(n-hexane:EtOAc=6:1) to give Y1.

General Procedure for the Synthesis of Y2

Target compound Y2 was synthesized according to general procedure forthe synthesis of A3.

General Procedure for the Synthesis of Y3

Target compound Y3 was synthesized according to general procedure forthe synthesis of A5-method 2.

General Procedure for the Synthesis of Y4

To a stirred solution of Y3 (0.94 mmol) in tetrahydrofuran (2.0 mL) wereadded sodium methoxide (0.14 mmol) and copper iodide (0.94 mmol) at 0°C. and the reaction mixture was stirred at room temperature forovernight. After reaction completion, the mixture was diluted withmethylene chloride (10 mL) and washed with brine (10 mL). The organiclayer was dried over anhydrous MgSO₄ and concentrated in vacuo. Theresulting crude residue was purified by flash column chromatography togive Y4.

General Procedure for the Synthesis of Y5

Target compound Y5 was synthesized according to general procedure forthe synthesis of H3.

General Procedure for the Synthesis of Z1-a and Z1-b

To a stirred solution of starting material (8.81 mmol) in toluene (20mL) were added N-bromosuccinimide (8.81 mmol) and p-toluenesulfonic acidmonohydrate (0.88 mmol) and then the resulting mixture was stirred at115° C. for 2 hours. The reaction mixture was diluted with methylenechloride (20 mL) and washed with brine (20 mL). The organic layer wasdried over anhydrous MgSO₄ and concentrated in vacuo. The crude productwas purified by flash column chromatography to give Z1-a or Z1-b.

General Procedure for the Synthesis of Z2-a and Z2-b

To a stirred solution of Z1-a or Z1-b (5.98 mmol) in EtOH (20 mL) wasadded thiourea (6.28 mmol) and the mixture was stirred at refluxtemperature for 2 hours. After reaction completion, the reaction mixturewas diluted with methylene chloride (20 mL) and washed with brine (20mL) The organic layer was dried over anhydrous MgSO₄ and concentrated invacuo to give Z2-a or Z2-b.

Z2-a; ¹H NMR (400 MHz, DMSO-d₆) δ 6.62 (brs, 2H, NH₂), 4.03-4.10 (m,2H), 2.59-2.72 (m, 2H), 2.39-2.44 (m, 2H), 1.99-2.03 (m, 1H), 1.69-1.79(m, 1H), 1.49-1.18 (m, 3H).Z2-b; ¹H NMR (400 MHz, CDCl₃) δ 4.77 (brs, 2H, NH₂), 4.42 (s, 2H),3.67-3.71 (m, 2H), 2.61-2.65 (m, 2H), 1.46 (s, 9H).

General Procedure for the Synthesis of Z3-a and Z3-b

To a stirred solution of Z2-a or Z2-b (5.87 mmol) in acetonitrile (20mL) were added copper(II)bromide (7.04 mmol) and tert-butyl nitrate(14.67 mmol). The reaction mixture was stirred at reflux temperature for3 hours. The reaction mixture was diluted with methylene chloride (20mL) and washed with brine (20 mL). The organic layer was dried overanhydrous MgSO₄ and concentrated in vacuo. The crude product waspurified by flash column chromatography to give Z3-a or Z3-b.

Z3-a; ¹H NMR (400 MHz, CDCl₃) δ 4.16-4.21 (m, 2H), 2.72-3.01 (m, 5H),2.21-2.27 (m, 1H), 1.95-2.01 (m, 1H), 1.22-1.28 (m, 3H).Z3-b; ¹H NMR (400 MHz, CDCl₃) δ 4.17-4.21 (m, 2H), 3.77-4.01 (m, 4H),3.39-3.42 (m, 4H), 2.85-2.89 (m, 2H), 2.59-2.79 (m, 3H), 2.18-2.24 (m,1H), 1.90-1.98 (m, 1H), 1.25-1.30 (m, 3H).

General Procedure for the Synthesis of Z4-a and Z4-b

Target compound Z4-a and Z4-b were synthesized according to generalprocedure for the synthesis of U6.

Z4-a; ¹H NMR (400 MHz, CDCl₃) δ 4.17-4.21 (m, 2H), 3.77-4.01 (m, 4H),3.39-3.42 (m, 4H), 2.85-2.89 (m, 2H), 2.59-2.79 (m, 3H), 2.18-2.24 (m,1H), 1.90-1.98 (m, 1H), 1.25-1.30 (m, 3H).Z4-b; ¹H NMR (400 MHz, CDCl₃) δ 4.44 (s, 2H), 3.78-3.80 (m, 4H),3.67-3.70 (m, 2H), 3.38-3.43 (m, 4H), 2.64-2.67 (m, 2H), 1.47 (m, 9H).

General Procedure for the Synthesis of Z5

To a stirred solution of Z4-b (0.020 g, 0.076 mmol) in 1, 4-dioxane (2.0mL) was added conc. HCl (10 uL) and the reaction mixture was stirred for3 hours. The solution was concentrated and dried under reduced pressure.The resulting residue was dissolved in methylene chloride (2.0 mL) andtriethylamine (32 uL, 0.23 mmol) and carbamate (0.026 g, 0.084 mmol)were added to the solution. After that, the resulting solution wasstirred for an hour at room temperature. After reaction completion, thesolution was diluted with methylene chloride (5 mL) and washed withwater (5 mL) The organic layer was dried over anhydrous MgSO₄ andconcentrated in vacuo to give Z5.

General Procedure for the Synthesis of AA1

To a stirred solution of 5-bromo-1,3,4-thiadiazol-2-amine (8.33 mmol) inethanol (20 mL) was added ethyl bromopyruvate (9.16 mmol). The reactionmixture was stirred at reflux temperature for 8 hours. After reactioncompletion, the reaction mixture was diluted with methylene chloride (20mL) and washed with brine (20 mL). The organic layer was dried overanhydrous MgSO₄ and concentrated in vacuo. The crude product waspurified by flash column chromatography to give AA1.

AA1; ¹H NMR (400 MHz, CDCl₃) δ 8.34 (s, 1H), 4.38-4.43 (m, 2H),1.38-1.44 (m, 3H).

General Procedure for the Synthesis of AB1

To a stirred solution of 2,4,5-tribromoimidazole (1.0 g, 3.28 mmol) intetrahydrofuran (15.0 mL) was added NaH (60% dispersion in paraffin,0.20 g, 4.92 mmol) under ice-bath. After 10 min, chloromethyl methyleter(0.30 mL, 3.94 mmol) was added slowly. The reaction mixture was allowedto room temperature and further stirred for 1.5 hours. The reactionmixture was quenched with water (20 mL) and extracted with EtOAc (20mL×2). The organic layer was dried over anhydrous MgSO₄ and concentratedin vacuo to give AB1.

General Procedure for the Synthesis of AB2

Target compound AB2 was synthesized according to general procedure forthe synthesis of U6. ¹H NMR (400 MHz, acetone-d₆) δ 5.23 (s, 2H),3.74-3.76 (m, 4H), 3.38 (s, 3H), 3.08-3.11 (m, 4H).

General Procedure for the Synthesis of AB3

To a stirred solution of AB2 (0.21 g, 0.59 mmol) in tetrahydrofuran (5.0mL) was added n-BuLi (2.5 M in n-hexane, 0.26 mL, 0.65 mmol) at −78° C.After 30 min, N,N-dimethylformamide (46 uL, 0.59 mmol) was added and theresulting mixture was stirred for 4 hours while maintaining temperaturebelow −60° C. The reaction mixture was quenched with water (5 mL) andextracted with EtOAc (5 mL×2). The organic solution was washed withbrine (5 mL), dried over anhydrous MgSO₄ and concentrated in vacuo. Thecrude residue was purified by flash column chromatography(n-hexane:EtOAc=3:1) to give AB3.

General Procedure for the Synthesis of AB4

To a stirred solution of AB3 (0.056 g, 0.18 mmol) in ethanol (3.0 mL)were added sodium ethoxide (20% in EtOH, 0.19 mL, 0.055 mmol) andethylthio glycolate (0.027 g, 0.22 mmol) and the reaction mixture wasstirred at room temperature for 2 hours. The reaction was quenched withwater (2 mL) and the resulting mixture was concentrated under reducedpressure. The crude residue was purified by flash column chromatography(n-hexane:EtOAc=3:1) to give AB4.

General Procedure for the Synthesis of AC1

To a stirred solution of ethyl 3-(4-nitrophenyl)-3-oxopropanoate (0.50g, 2.11 mmol) in EtOH (7.0 mL) was added hydrazine hydrate (0.12 mL,2.53 mmol). The reaction mixture was stirred at 90° C. for 3 hours.After reaction completion, the mixture was evaporated and H₂O (10 mL)was added. The residual pale solid was collected by filtration, washedwith water and dried in vacuo to give AC1 (165 mg, yield=38%).

General Procedure for the Synthesis of AC2

To a stirred solution AC1 (165 mg, 0.80 mmol) in anhydrous DMF (5.0 mL)were added dibromoethane (0.076 mL, 0.88 mmol) and K₂CO₃ (445 mg, 3.22mmol). The reaction mixture was stirred at 70° C. for 12 hours. Thereaction mixture was cooled to room temperature and then water (10 mL)was poured. The residual pale solid was collected by filtration anddried in vacuo to give AC2 (163 mg, yield=88%).

General Procedure for the Synthesis of AD1

To a stirred solution of tert-butyl2-bromo-6,7-dihydrothieno[3,2-c]pyridine-5(4H)-carboxylate (0.070 g,0.22 mmol) in 2-(dimethylamino)ethanol (1.0 mL) were added morpholine(0.095 mL, 1.10 mmol), CuI (0.0042 g, 0.022 mmol), Cu (0.0014 g, 0.022mmol) and K₃PO₄ (0.12 g, 0.55 mmol). The reaction mixture was stirred at100° C. for 3 days. After reaction completion, the reaction mixture wasdiluted with dichloromethane (5 mL) and washed with brine (5 mL). Theorganic layer was dried over anhydrous MgSO₄ and concentrated in vacuo.The crude product was purified by flash column chromatography to giveAD1 (33.4 mg, yield=47%).

General Procedure for the Synthesis of AE1

To a stirred solution of 2N HCl in diethylether:MeOH=1:1 (8.0 mL) wasadded 2-chloroacetonitrile (0.17 ml, 2.65 mmol) at 0° C. The reactionmixture was stirred at room temperature for 12 hours. After reactioncompletion, the reaction mixture was concentrated. The resulting residuewas dissolved in methylene chloride (3.0 mL) and 2-amino-4-nitrophenol(20 mg, 0.13 mmol) was added at 0° C. The reaction mixture was stirredat room temperature for 2 hours and then the reaction temperature wasraised to 45° C. After 4 hours, the mixture was evaporated and methanolwas added to the resulting residue. The insoluble solid was filtered offand the filtrate was concentrated and purified by flash columnchromatography to give AE1.

General Procedure for the Synthesis of AE2

To a stirred solution of AE1 (29 mg, 0.14 mmol) in N,N-dimethylformamide(0.3 mL) was added morpholine (0.18 ml, 2.05 mmol). The reaction mixturewas stirred at room temperature for 12 h. The reaction mixture wasdiluted with EtOAC (5 mL) and washed with brine (5 mL). The organiclayer was dried over anhydrous MgSO₄ and concentrated in vacuo. Thecrude product was purified by flash column chromatography to give AE2(19 mg, yield=53%).

General Procedure for the Synthesis of AF1

To a stirred solution of 4-hydroxy-3-nitrobenzaldehyde (0.50 mg, 2.99mmol) in acetonitrile (15 mL) was added(carbethoxymethylene)triphenylphosphorane (1.15 mg, 3.29 mmol). Thereaction mixture was stirred at 80° C. for 5 h. After reaction wascompleted, the reaction mixture was diluted with EtOAC (20 mL) andwashed with brine (15 mL). The organic layer was dried over anhydrousMgSO₄ and concentrated in vacuo. The crude product was purified by flashcolumn chromatography to give AF1 (488 mg, yield=69%).

General Procedure for the Synthesis of AF2

Target compound AF2 was synthesized according to general procedure forthe synthesis of E3 & E7.

General Procedure for the Synthesis of AF3

Target compound AF3 was synthesized according to general procedure forthe synthesis of E2 & E5.

General Procedure for the Synthesis of AF4

To a stirred solution of AF3 (0.15 g, 0.64 mmol) in THF (2.0 mL) andMeOH (0.2 mL) and H₂O (1.0 ml) was added lithium hydroxide (77 mg, 3.22mmol). The mixture was stirred at room temperature for overnight. Afterreaction completion, the mixture was evaporated and 1 N HCl (10 mL) wasadded until pH was reached to 5. The residual pale solid was collectedby filtration, washed with water and dried in vacuo to give AF4 (67 mg,yield=51%).

General Procedure for the Synthesis of AF5

Target compound AF5 was synthesized according to general procedure forthe synthesis of X1.

General Procedure for the Synthesis of AG1

To a solution of nitrile starting material (60 mg, 0.38 mmol) andnickel(II) chloride hexahydrate (135 mg, 0.57 mmol) in EtOH (4.8 ml) wasadded sodium borohydride (43 mg, 1.14 mmol) portionwise under ice bath.The reaction mixture was warmed to room temperature slowly and thefurther stirred for 1.5 h. After reaction completion, the mixture wasquenched with water, diluted with dichloromethane, dried over MgSO₄ andconcentrated to give mixture of desired amine AG1 and dimer (2:1 ratio,42%). The resulting crude residue was used for next reaction withoutfurther purification.

General Procedure for the Synthesis of AH1

To a stirred solution of ethyl2-((2-hydroxyethyl)(methyl)amino)thieno[2,3-d]thiazole-5-carboxylate(0.50 g, 1.7 mmol) in DMF (5 mL) was added sodium hydride (0.084 g, 2.1mmol) at 0° C. After 15 min, 2-iodopropane (0.89 g, 5.2 mmol) was addedand then the resulting mixture was further stirred for 3 h at roomtemperature. The reaction mixture was quenched with water (10 ml) andextracted with dichloromethane (30 mL×3). The organic layer was driedover anhydrous Na₂SO₄ and concentrated in vacuo. The resulting cruderesidue was purified by flash column chromatography (n-hexane:EtOAc=3:1)to give AH1.

General Procedure for the Synthesis of AI1

To a stirred solution of 2,4-dichloro-5-(1,3-dioxolan-2-yl) thiazole(0.91 g, 4.0 mmol) in DMF (15 mL) was added sodium hydride (0.20 g, 5.0mmol) under ice bath. After stirring for 5 min, cyclohexanol (0.34 g,3.4 mmol) was slowly added and then the reaction mixture was furtherstirred for overnight at room temperature. After reaction completion,the mixture was quenched with water (10 ml) and extracted withdichloromethane (30 mL×3). The organic layer was dried over anhydrousNa₂SO₄ and concentrated in vacuo. The resulting crude residue waspurified by flash column chromatography (n-hexane:EtOAc=10:1) to give

General Procedure for the Synthesis of AJ2

To a stirred solution of N,N-dimethylpiperidine-4-carboxamidetrifluoroacetic acid (0.085 mg, 0.55 mmol) in acetonitrile (1.2 mL) wasadded potassium carbonate (0.22 g, 1.56 mmol) at room temperature. Afterstirring for 10 min, AJ1 (0.146 g, 0.31 mmol) was added and then themixture was further stirred at 50° C. for overnight. The reactionmixture was quenched with water (20 mL) and extracted with ethylacetate(20 mL×2). The organic layer was dried over MgSO₄ and concentrated invacuo. The resulting crude residue was purified by flash columnchromatography (dichloromethane:methanol=50:1 ratio) to give AJ2.

REFERENCES

-   Andries K. et al. A diarylquinoline drug active on the ATP synthase    of Mycobacterium tuberculosis (2005). Science 307, 223-227.-   Arain, T. M., Resconi, A. E., Singh, D. C., and Stover, C. K.    (1996). Reporter gene technology to assess activity of    antimycobacterial agents in macrophages. Antimicrob Agents Chemother    40, 1542-1544.-   Brodin, P., Christophe, T., No, Z., Kim, J., Genovesio, A.,    Fenistein, D. P. C., Jeon, H., Ewann, F. A., Kang, S., Lee, S.,    Seo, M. J., Park, E., Contreras Dominguez, M., Nam, J., Kim, E.    Anti-Infective Compounds. WO2010003533A1.-   Chaisson, R. E. & Nuermberger, E. L. Confronting multidrug-resistant    tuberculosis (2012). N Engl J Med 366, 2223-2224-   Diacon, A. H. et al. Randomized pilot trial of eight weeks of    bedaquiline (TMC207) treatment for multidrug-resistant tuberculosis:    long-term outcome, tolerability, and effect on emergence of drug    resistance (2012). Antimicrob Agents Chemother 56, 3271-3276-   Gler, M. T. et al. Delamanid for multidrug-resistant pulmonary    tuberculosis (2012). N Engl J Med 366, 2151-2160-   Houben, E. N., Nguyen, L., and Pieters, J. (2006). Interaction of    pathogenic mycobacteria with the host immune system. Curr Opin    Microbiol 9, 76-85.-   Pethe, K. et al. Discovery of Q203, a potent clinical candidate for    the treatment of tuberculosis (2013). Nat Med. 19(9), 1157-1160-   Rohde, K. H., Abramovitch, R. B., and Russell, D. G. (2007).    Mycobacterium tuberculosis invasion of macrophages: linking    bacterial gene expression to environmental cues. Cell Host Microbe    2, 352-364.-   Stanley, S. A. et al. Identification of novel inhibitors of M.    tuberculosis growth using whole cell based high-throughput screening    (2012). ACS Chem Biol 7, 1377-1384.-   Stover, C. K., Arrener, P., VanDevanter, D. R., Sherman, D. R.,    Arain, T. M., Langhorne, M. H., Anderson, S. W., Towell, J. A.,    Yuan, Y., McMurray, D. N., Kreiswirth, B. N., Barry, C. E.,    Baker, W. R. (2000). A small-molecule nitroimidazopyran drug    candidate for the treatment of tuberculosis. Naure 405, 962-6.

The invention is now further described by reference to tables 1-3.

TABLE 1 Structures and characteristics of compounds 1-360 No. StructureNMR Characterization  1

White solid; mp = 196° C.; ¹H NMR (400 MHz, acetone- d₆) δ 8.16 (d, J =1.6 Hz, 1H), 7.74 (dd, J = 8.4 Hz, 1.6 Hz, 1H), 7.61 (brs, 1H), 7.39 (d,J = 8.4 Hz, 1H), 7.28-7.31 (m, 4H), 7.18-7.21 (m, 1H), 3.62-3.65 (m,4H), 3.54- 3.58 (m, 2H), 3.13-3.18 (m, 1H), 1.66-1.70 (m, 6H), 1.30 (d,J = 6.8 Hz, 3H); LCMS (electrospray) m/z 380 (M + H)⁺.  2

Pale yellow solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.36 (brs, 1H), 7.89(s, 1H), 7.66-7.68 (m, 2H), 6.90-6.94 (m, 2H), 3.79 (s, 3H), 3.52-3.57(m, 4H), 1.66-1.72 (m, 6H); LCMS (electrospray) m/z 374 (M + H)⁺.  3

Yellow solid; mp = 246.3° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.65 (brs,1H), 7.93-7.97 (m, 1H), 7.91 (s, 1H), 7.46-7.51 (m, 1H), 7.27-7.34 (m,1H), 3.50- 3.60 (m, 4H), 1.64-1.74 (m, 6H); LCMS (electrospray) m/z 380(M + H)⁺.  4

Yellow solid; mp = 231.2° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.38 (brs,1H), 7.91 (s, 1H), 7.06-7.07 (m, 2H), 6.26-6.27 (m, 1H0, 3.78 (s, 6H),3.52-3.58 (m, 4H), 1.68-1.72 (m, 6H); LCMS (electrospray) m/z 404 (M +H)⁺.  5

White solid; mp = 214° C.; ¹H NMR (400 MHz, acetone- d₆) δ 9.32 (s, 1H,NH), 8.33 (d, J = 2.0 Hz, 1H), 7.93 (dd, J = 8.4 Hz, 2.0 Hz, 1H), 7.75(d, J = 9.2 Hz, 2H), 7.46 (d, J = 8.4 Hz, 1H), 6.92 (d, J = 9.2 Hz, 2H),3.79 (s, 3H), 3.66- 3.68 (m, 4H), 1.69-1.74 (m, 6H); LCMS (electrospray)m/z 368 (M + H)⁺.  6

Pale yellow solid; mp = 274° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.64 (s,1H, NH), 8.89 (s, 2H), 7.90 (s, 1H), 3.95 (s, 3H), 3.54-3.56 (m, 4H),1.68-1.72 (m, 6H); LCMS (electrospray) m/z 376 (M + H)⁺.  7

Ivory solid; mp = 179° C.; ¹H NMR (400 MHz, acetone-d₆) δ 8.10 (brs, 1H,NH), 7.74 (s, 1H), 7.29 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 8.4 Hz, 2H),4.49 (d, J = 6.0 Hz, 2H), 3.77 (s, 3H), 3.52-3.54 (m, 4H), 1.66-1.70 (m,6H); LCMS (electrospray) m/z 388 (M + H)⁺.  8

Yellow solid; mp = 218° C.; ¹H NMR (400 MHz, acetone- d₆) δ 9.53 (s, 1H,NH), 7.90 (s, 1H), 7.79 (dd, J = 8.8 Hz, 5.2 Hz, 2H), 7.12 (dd, J = 8.8Hz, 8.8 Hz, 2H), 3.54-3.56 (m, 4H), 1.68-1.71 (m, 6H); LCMS(electrospray) m/z 362 (M + H)⁺.  9

Ivory solid; mp = 153° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.96 (s, 1H), 7.01(d, J = 8.8 Hz, 2H), 6.70 (d, J = 8.8 Hz, 2H), 3.65 (brs, 2H, NH2),3.52-3.55 (m, 4H), 1.66-1.71 (m, 6H); LCMS (electrospray) m/z 359 (M +H)⁺.  10

Orange solid; mp = 270° C.; ¹H NMR (400 MHz, acetone- d₆) δ 9.51 (s, 1H,NH), 8.48 (d, J = 2.4 Hz, 1H), 8.04 (dd, J = 8.0, 2.4 Hz, 1H), 7.88 (s,1H), 6.77 (d, J = 8.8 Hz, 1H), 3.87 (s, 3H), 3.52-3.56 (m, 4H),1.67-1.71 (m, 6H); LCMS (electrospray) m/z 374 (M + H)⁺.  11

Ivory solid; mp = 223° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.38 (s, 1H,NH), 7.88 (s, 1H), 7.68 (d, J = 9.2 Hz, 2H), 7.45-7.51 (m, 2H),7.30-7.41 (m, 3H), 7.02 (d, J = 9.2 Hz, 2H), 5.12 (s, 2H), 3.52-3.56 (m,4H), 1.67-1.71 (m, 6H); LCMS (electrospray) m/z 449 (M + H)⁺.  12

¹H NMR (400 MHz, acetone-d₆) δ 9.40 (s, 1H, NH), 7.90 (s, 1H), 7.67 (d,J = 8.8 Hz, 2H), 7.19 (d, J = 8.8 Hz, 2H), 3.52-3.56 (m, 4H), 2.60 (q, J= 7.6 Hz, 2H), 1.67-1.71 (m, 6H), 1.20 (t, J = 7.6 Hz, 3H); LCMS(electrospray) m/z 371 (M + H)⁺.  13

¹H NMR (400 MHz, acetone-d₆) δ 9.76 (s, 1H, NH), 8.00 (d, J = 8.8 Hz,2H), 7.97 (s, 1H), 7.91 (d, J = 8.8 Hz, 2H), 3.86 (s, 3H), 3.53-3.58 (m,4H), 1.66-1.71 (m, 6H); LCMS (electrospray) m/z 401 (M + H)⁺.  14

Pale yellow solid; mp = 238.0° C.; ¹H NMR (400 MHz, acetone-d₆) δ 7.97(brs, 1H), 7.75 (s, 1H), 7.67 (d, J = 8.8 Hz, 2H), 7.21 (d, J = 8.8 Hz,2H), 3.58-3.61 (m, 4H), 1.71- 1.74 (m, 6H); LCMS (electrospray) m/z 428(M + H)⁺.  15

Pale yellow solid; mp = 225.8° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.51(s, 1H),k 7.91 (s, 1H), 7.77-7.79 (m, 2H), 7.35-7.39 (m, 2H), 7.09-7.13(m, 1H), 7.00-7.02 (m, 4H), 3.53-3.55 (m, 4H), 1.68-1.70 (m, 6H); LCMS(electrospray) m/z 436 (M + H)⁺.  16

Ivory solid; mp = 194° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.73 (s, 1H,NH), 8.32 (s, 1H), 8.03-8.09 (m, 3H), 7.57- 7.62 (m, 2H), 7.24-7.32 (m,2H), 3.80-3.84 (m, 4H), 1.63-1.73 (m, 6H); LCMS (electrospray) m/z 368(M + H)⁺.  17

White solid; mp = 209° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.42 (s, 1H,NH), 8.31 (s, 1H), 8.10 (d, J = 9.6 Hz, 1H), 8.05 (d, J = 9.2 Hz, 1H),7.79 (d, J = 8.8 Hz, 2H), 7.62 (d, J = 9.2 Hz, 1H), 7.25 (d, J = 9.6 Hz,1H), 6.94 (d, J = 8.8 Hz, 2H), 3.81 (s, 3H), 3.79-3.84 (m, 4H),1.64-1.74 (m, 6H); LCMS (electrospray) m/z 362 (M + H)⁺.  18

Ivory solid; mp = 266° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.31 (s, 1H,NH), 8.20 (s, 1H, OH), 7.87 (s, 1H), 7.57 (d, J = 8.8 Hz, 2H), 6.82 (d,J = 8.8 Hz, 2H), 3.53-3.56 (m, 4H), 1.67-1.71 (m, 6H); LCMS(electrospray) m/z 359 (M + H)⁺.  19

¹H NMR (400 MHz, DMSO-d₆) δ 10.40 (s, 1H, NH), 8.17 (s, 1H), 7.95 (d, J= 8.0 Hz, 2H), 7.79 (d, J = 8.8 Hz, 2H), 3.50-3.54 (m, 4H), 1.62-1.67(m, 6H); LCMS (electrospray) m/z 387 (M + H)⁺.  20

Pale yellow solid; mp = 170.1° C.; ¹H NMR (400 MHz, acetone-d₆) δ7.50-7.56 (m, 1H), 7.43-7.48 (m, 1H), 7.29-7.31 (m, 1H), 6.51 (s, 1H),3.42-3.48 (m, 4H), 3.38 (s, 3H), 1.58-1.68 (m, 6H); LCMS (electrospray)m/z 394 (M + H)⁺.  21

White solid; mp = 236.0° C.; ¹H NMR (400 MHz, acetone- d₆) δ 9.60 (brs,1H, NH), 9.20 (s, 1H), 8.32 (s, 1H), 7.70 (d, J = 8.8 Hz, 2H), 6.94 (d,J = 8.8 Hz, 2H), 3.80 (s, 3H); LCMS (electrospray) m/z 291 (M + H)⁺.  22

White solid; mp = 188.0° C.; ¹H NMR (400 MHz, acetone- d₆) δ 7.77 (s,1H), 7.65 (s, 1H), 7.16-7.65 (m, 2H), 6.84- 6.87 (m, 2H), 3.76 (s, 3H),3.56-3.57 (m, 2H), 3.52- 3.54 (m, 4H), 2.78-2.85 (m, 2H), 1.68-1.69 (s,6H); LCMS (electrospray) m/z 401 (M + H)⁺.  23

Yellow solid; mp = 260° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 10.32 (s, 1H,NH), 10.05 (s, 1H, NH), 8.00 (s, 1H), 7.58 (s, 1H), 7.43 (d, J = 8.4 Hz,1H), 6.77 (d, J = 8.4 Hz, 1H), 3.46-3.49 (m, 6H), 1.58-1.61 (m, 6H);LCMS (electrospray) m/z 399 (M + H)⁺.  24

Colorless oil; ¹H NMR (400 MHz, acetone-d₆) δ 7.36 (s, 1H), 4.33-4.36(m, 2H), 3.67 (s, 3H), 3.52-3.54 (m, 4H), 3.20-3.25 (m, 2H), 2.69-2.75(m, 1H), 1.98-2.01 (m, 2H), 1.67-1.70 (m, 8H); LCMS (electrospray) m/z394 (M + H)⁺.  25

Pale yellow solid; mp = 222.6° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.48(brs, 1H, NH), 7.93 (s, 1H), 7.77-7.79 (m, 2H), 7.33-7.37 (m, 2H),7.09-7.12 (m, 1H), 3.52- 3.58 (m, 4H), 1.66-1.76 (m, 6H); LCMS(electrospray) m/z 344 (M + H)⁺.  26

Pale yellow solid; mp = 188.0° C.; ¹H NMR (400 MHz, acetone-d₆) δ 7.39(s, 1H, NH), 3.74-3.80 (m, 4H), 3.68- 3.73 (m, 4H), 3.48-3.57 (m, 4H),1.64-1.72 (m, 6H); LCMS (electrospray) m/z 338 (M + H)⁺.  27

Pale yellow solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.41 (s, 1H), 7.93 (s,1H), 7.67 (d, J = 8.8 Hz, 2H), 6.92 (d, J = 8.8 Hz, 2H), 3.77-3.79 (m,7H), 3.52-3.58 (m, 4H); LCMS (electrospray) m/z 375 (M + H)⁺.  28

Yellow solid; mp = 289° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 10.33 (s, 1H,NH), 8.35 (q, J = 4.4 Hz, 1H, NH), 8.20 (s, 1H), 7.86 (d, J = 9.2 Hz,2H), 7.81 (d, J = 9.2 Hz, 2H), 3.59-3.61 (m, 4H), 2.81 (d, J = 4.4 Hz,3H), 1.67-1.69 (m, 6H); LCMS (electrospray) m/z 401 (M + H)⁺.  29

Yellow solid; mp = 230° C.; ¹H NMR (400 MHz, acetone- d₆) δ 9.58 (s, 1H,NH), 7.91 (s, 1H), 7.81 (d, J = 8.8 Hz, 2H), 7.37 (d, J = 8.8 Hz, 2H),3.53-3.57 (m, 4H), 1.67- 1.71 (m, 6H); LCMS (electrospray) m/z 377 (M +H)⁺.  30

White solid; mp = 191° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.42 (s, 1H), 5.85(brs, 1H, NH), 4.06-4.12 (m, 1H), 3.70 (s, 3H), 3.48-3.52 (m, 4H),2.52-2.58 (m, 1H), 1.86- 1.96 (m, 2H), 1.80-1.85 (m, 2H), 1.73-1.78 (m,2H), 1.66-1.70 (m, 6H), 1.61-1.64 (m, 2H); LCMS (electrospray) m/z 408(M + H)⁺.  31

Pale yellow solid; mp = 178.5° C.; ¹H NMR (400 MHz, acetone-d₆) δ 8.10(d, J = 8.4 Hz, 2H), 7.53 (d, mJ = 8.4 Hz, 2H), 6.41 (s, 1H), 3.91 (s,3H), 3.42-3.47 (m, 7H), 1.58- 1.67 (m, 6H); LCMS (electrospray) m/z 416(M + H)⁺.  32

Orange solid; mp = 163° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 10.50 (s,l 1H,NH), 8.08 (s, 1H), 7.92 (d, J = 8.8 Hz, 2H), 7.80 (d, J = 8.8 Hz, 2H),3.46-3.49 (m, 4H), 1.59- 1.62 (m, 6H); LCMS (electrospray) m/z 369 (M +H)⁺.  33

Pale yellow solid; mp = 228.6° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.78(s, 1H), 8.01 (d, J = 8.8 Hz, 2H), 7.97 (s, 1H), 7.70 (d, J = 8.8 Hz,2H), 3.54-3.56 (m, 4H), 1.68- 1.69 (m, 6H); LCMS (electrospray) m/z 411(M + H)⁺.  34

Dark yellow solid; mp = 213.0° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.68(brs, 1H, NH), 8.27-8.28 (m, 1H), 7.95 (s, 1H), 7.53-7.54 (m, 2H),3.52-3.58 (m, 4H), 2.59 (s, 3H), 1.68-1.73 (m, 6H); LCMS (electrospray)m/z 399 (M + H)⁺.  35

Ivory solid; mp = 235° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.01 (s, 1H,NH), 8.08 (s, 1H), 7.59 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 8.8 Hz, 2H),3.73 (s,k 3H), 3.52-3.56 (m, 4H), 1.61-1.65 (m, 6H); LCMS (electrospray)m/z 373 (M + H)⁺.  36

Yellow solid; mp = 218° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 10.31 (s, 1H,NH), 8.16 (s, 1H), 7.82-7.89 (m, 1H), 7.37-7.49 (m, 2H), 3.50-3.58 (m,4H), 1.59-1.68 (m, 6H); LCMS (electrospray) m/z 379 (M + H)⁺.  37

Yellow solid; mp = 148° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 10.02 (s, 1H,NH), 8.11 (s, 1H), 6.99 (s, 1H), 6.98 (s, 1H), 6.23 (s, 1H), 3.73 (s,6H), 3.52-3.56 (m, 4H), 1.61- 1.65 (m, 6H); LCMS (electrospray) m/z 403(M + H)⁺.  38

Brown solid; mp = 198.0° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.68-7.70 (m,2H), 7.52 (d, J = 8.0 Hz, 2H), 7.16 (d, J = 8.0 Hz, 2H), 3.57-3.61 (m,4H), 2.60 (q, J = 7.2 Hz, 2H), 1.69-1.71 (m, 6H), 1.20 (t, J = 7.2 Hz,3H); LCMS (electrospray) m/z 372 (M + H)⁺.  39

Orange solid; mp = 231.1° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 10.21 (s,1H), 8.16 (s, 1H), 7.80 (d, J = 8.8 Hz, 2H), 7.65-7.67 (m, 4H),7.43-7.47 (m, 2H), 7.31-7.35 (m, 1H), 3.54-3.56 (m, 4H), 1.62-1.64 (m,6H); LCMS (electrospray) m/z 420 (M + H)⁺.  40

Pale yellow solid; mp = 279.5° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.44 (s,1H), 8.78 (dd, J = 4.0, 1.6 Hz, 1H), 8.41 (s, 1H), 8.28 (dd, J = 8.4,1.6 Hz, 1H), 8.21 (s, 1H), 8.00-8.01 (m, 2H), 7.47 (dd, J = 8.4, 4.0 Hz,1H), 3.55- 3.57 (m, 4H), 1.63-1.65 (m, 6H); LCMS (electrospray) m/z 395(M + H)⁺.  41

Pale green solid; mp = 289.2° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.68(s, 1H), 8.00-8.01 (m, 3H), 7.68-7.69 (m, 2H), 3.61-3.62 (m, 4H),2.77-2.81 (m, 2H), 1.71- 1.72 (m, 4H); LCMS (electrospray) m/z 411 (M +H)⁺.  42

Pale yellow solid; mp = 177.2° C.; ¹H NMR (400 MHz, acetone-d₆) δ 7.69(s, 1H), 7.59 (s, 1H), 7.17 (d, J = 8.4 Hz, 2H), 6.85 (d, J = 8.4 Hz,2H), 3.76 (s, 3H), 3.55-3.58 (m, 4H), 3.51-3.53 (m, 2H), 2.81-2.84 (m,2H), 1.67- 1.69 (m, 6H); LCMS (electrospray) m/z 401 (M + H)⁺.  43

Pale yellow solid; mp = 212.9° C.; ¹H NMR (400 MHz, acetone-d₆) δ 7.93(d, J = 8.0 Hz, 2H), 7.68 (s, 1H), 7.67 (s, 1H), 7.40 (d, J = 8.0 Hz,2H), 3.86 (s, 3H), 3.62-3.65 (m, 2H), 3.57-3.60 (m, 4H), 2.97-3.01 (m,2H), 1.67-1.69 (m, 6H); LCMS (electrospray) m/z 429 (M + H)⁺.  44

Pale yellow solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.28 (s, 1H), 7.93 (s,1H), 7.67 (d, J = 8.8 Hz, 2H), 7.48-7.49 (m, 2H), 7.38-7.41 (m, 2H),7.31-7.34 (m, 1H), 6.99 (d, J = 8.8 Hz, 2H), 5.12 (s, 2H), 3.60-3.61 (m,4H), 1.71- 1.72 (m, 6H); LCMS (electrospray) m/z 449 (M + H)⁺.  45

Pale yellow solid; mp = 275.2° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.48(brs, 1H, NH), 7.96 (s, 1H), 7.79 (d, J = 8.0 Hz, 2H), 7.35 (d, J = 8.0Hz, 2H), 3.58-3.63 (m, 4H), 1.68-1.74 (m, 6H); LCMS (electrospray) m/z378, 380 (M + H)⁺ (Cl⁻ isotope pattern).  46

Pale yellow solid; mp = 259.1° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.36(brs, 1H, NH), 7.97 (s, 1H), 7.75-7.77 (m, 2H), 7.31-7.35 (m, 2H),7.06-7.10 (m, 1H), 3.58- 3.63 (m, 4H), 1.68-1.73 (m, 6H); LCMS(electrospray) m/z 344 (M + H)⁺.  47

Pale yellow solid; mp = 232.4° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.41(brs, 1H, NH), 8.47 (s, 1H), 8.05 (d, J = 8.8 Hz, 1H), 7.94 (s, 1H),6.76 (d, J = 8.8 Hz, 1H), 3.87 (s, 3H), 3.58-3.63 (m, 4H), 1.66-1.74 (m,6H); LCMS (electrospray) m/z 375 (M + H)⁺.  48

Pale yellow solid; mp = 259.2° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.58(brs, 1H, NH), 8.26 (s, 1H), 8.00 (s, 1H), 7.51-7.54 (m, 2H), 3.58-3.63(m, 4H), 2.58 (s, 3H), 1.66-1.74 (m, 6H); LCMS (electrospray) m/z 399(M + H)⁺.  49

Yellow solid; mp = 243° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 10.46 (s, 1H,NH), 8.23 (s, 1H), 7.99 (d, J = 8.8 Hz, 2H), 7.91 (d, J = 8.8 Hz, 2H),3.87 (s, 3H), 3.59-3.61 (m, 4H), 1.67-1.69 (m, 6H); LCMS (electrospray)m/z 402 (M + H)⁺.  50

Pale yellow solid; mp = 326° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.68 (s,1H),l 7.97 (s, 1H), 7.84-7.91 (m, 2H), 1.94-2.01 (m, 4H), 1.70 (s, 3H);LCMS (electrospray) m/z 400 (M + H)⁺.  51

¹H NMR (400 MHz, DMSO-d₆) δ 10.34 (s, 1H), 8.23 (s, 1H), 7.90 (d, J =8.0 Hz, 2H), 7.75 (d, J = 8.0 Hz, 2H), 3.53-3.54 (m, 4H), 1.61-1.62 (m,6H); LCMS (electrospray) m/z 387 (M + H)⁺.  52

Pale brown solid; mp = 202° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.04 (s,1H), 8.12 (s, 1H), 7.63 (d, J = 8.8 Hz, 2H), 6.96 (d, J = 8.8 Hz, 2H),3.78 (s, 3H), 3.18 (s, 6H); LCMS (electrospray) m/z 333 (M + H)⁺.  53

Yellow solid; mp = 233° C.; ¹H NMR (400 MHz, acetone- d₆) δ 9.43 (s, 1H,NH), 7.95 (s, 1H), 7.76-7.80 (m, 2H), 7.11 (dd, J = 8.8 Hz, 8.8 Hz, 2H),3.58-3.62 (m, 4H), 1.69- 1.72 (m, 6H); LCMS (electrospray) m/z 362 (M +H)⁺.  54

Yellow solid; mp = 177° C.; ¹H NMR (400 MHz, acetone- d₆) δ 9.74 (s, 1H,NH), 8.02 (s, 1H), 7.99 (d, J = 8.8 Hz, 2H), 7.73 (d, J = 8.8 Hz, 2H),3.60-3.63 (m, 4H), 1.70- 1.73 (m, 6H); LCMS (electrospray) m/z 369 (M +H)⁺.  55

Yellow solid; mp = 219° C.; ¹H NMR (400 MHz, acetone- d₆) δ 9.56 (s, 1H,NH), 8.88 (s, 2H), 7.96 (s, 1H), 3.94 (s, 3H), 3.60-3.63 (m, 4H),1.70-1.72 (m, 6H); LCMS (electrospray) m/z 376 (M + H)⁺.  56

Yellow solid; mp = 136° C.; ¹H NMR (400 MHz, acetone- d₆) δ 7.51 (s,1H), 4.32-4.36 (m, 2H), 3.66 (s, 3H), 3.56- 3.59 (m, 4H), 3.16-3.23 (m,2H), 2.68-2.73 (m, 1H), 1.98-2.00 (m, 2H), 1.64-1.74 (m, 8H); LCMS(electrospray) m/z 394 (M + H)⁺.  57

Ivory solid; mp = 84° C.; ¹H NMR (400 MHz, acetone-d₆) δ 7.52 (s, 1H),3.55-3.62 (m, 8H), 1.65-1.69 (m, 6H), 1.24 (t, J = 7.2 Hz, 6H); LCMS(electrospray) m/z 323 (M + H)⁺.  58

Yellow solid; mp = 239° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.32 (s, 1H,NH), 8.13 (s, 1H), 7.82 (d, J = 8.4 Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H),3.53-3.57 (m, 4H), 1.61-1.65 (m, 6H); LCMS (electrospray) m/z 427 (M +H)⁺.  59

Yellow solid; mp = 142° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 8.84 (t, J =8.0 Hz, 1H, NH), 7.87 (s, 1H), 7.24 (d, J = 8.8 Hz, 2H), 6.89 (d, J =8.8 Hz, 2H), 4.36 (d, J = 8.8 Hz, 2H), 3.72 (s, 3H), 3.49-3.55 (m, 4H),1.60-1.65 (m, 6H); LCMS (electrospray) m/z 387 (M + H)⁺.  60

Yellow solid; mp = 74° C.; ¹H NMR (400 MHz, acetone-d₆) δ 7.78 (s, 1H),7.29 (brs, 1H, NH), 3.95-3.99 (m, 1H), 3.64 (s, 3H), 3.54-3.60 (m, 4H),2.57-2.59 (m, 1H), 1.57- 1.77 (m, 14H); LCMS (electrospray) m/z 408 (M +H)⁺.  61

Orange solid; mp = 201° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 10.15 (s, 1H,NH), 8.11 (s, 1H), 7.71 (d, J = 9.2 Hz, 2H), 7.35-7.39 (m, 2H),6.98-7.04 (m, 5H), 3.52-3.57 (m, 4H), 1.61-1.65 (m, 6H); LCMS(electrospray) m/z 435 (M + H)⁺.  62

Ivory solid; mp = 195° C.; ¹H NMR (400 MHz, acetone-d₆) δ 7.29 (d, J =7.6 Hz, 2H), 7.02 (d, J = 7.6 Hz, 2H), 6.72 (s, 1H), 3.85 (s, 3H),3.46-3.52 (m, 4H), 3.18 (s, 3H), 1.61- 1.69 (m, 6H); LCMS (electrospray)m/z 387 (M + H)⁺.  63

While solid; mp = 243° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 9.96 (s, 1, NH),8.76 (t, J = 5.6 Hz, 1H, NH), 8.00 (s, 1H), 7.57 (d, J = 8.8 Hz, 2H),7.29 (d, J = 8.8 Hz, 2H), 6.88-6.91 (m, 4H), 4.47 (d, J = 5.6 Hz, 2H),3.72 (s, 6H); LCMS (electrospray) m/z 426 (M + H)⁺.  64

Grey solid solid; mp = 260° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.28 (s,1H, NH), 7.89 (s, 1H), 7.66 (d, J = 8.8 Hz, 2H), 7.08 (s, 2H, NH), 6.90(d, J = 8.8 Hz, 2H), 3.78 (s, 3H); LCMS (electrospray) m/z 306 (M + H)⁺. 65

Ivory solid; mp = 271° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.47 (s, 1H,NH), 8.09 (s, 1H), 7.69 (d, J = 8.8 Hz, 2H), 6.92 (d, J = 8.8 Hz, 2H),3.79 (s, 3H), 2.63-2.68 (m, 1H), 1.96-2.01 (m, 2H), 1.81-1.84 (m, 2H),1.69-1.72 (m, 1H), 1.51-1.60 (m, 2H), 1.26-1.40 (m, 3H); LCMS(electrospray) m/z 416 (M + H)⁺.  66

Pale brown solid; mp = 248.8° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.32(s, 1H), 7.96 (s, 1H), 7.66 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 8.8 Hz,2H), 3.79-3.81 (m, 4H), 3.78 (s, 3H), 3.57-3.59 (m, 4H); LCMS(electrospray) m/z 375 (M + H)⁺.  67

Pale yellow solid; mp = 105° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.24 (brs,1H, NH), 8.14 (s, 1H), 7.75 (d, J = 8.8 Hz, 2H), 7.39 (d, JU = 8.8 Hz,2H) 3.52-3.66 (m, 4H), 2.95 (s, 6H), 1.58-1.64 (m, 6H); LCMS(electrospray) m/z 415 (M + H)⁺.  68

Pale yellow solid; mp = 175° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.66 (s, 1H),7.58 (brs, 1H, NH), 7.52 (d, J = 8.8 Hz, 2H), 6.88 (d, J = 8.8 Hz, 2H),4.37-4.40 (m, 1H), 3.80 (s, 3H),l 3.02 (s, 3H), 1.28 (s, 6H); LCMS(electrospray) m/z 362 (M + H)⁺.  69

Yellow solid; mp = 105° C.; ¹H NMR (400 MHz, acetone- d₆) δ 7.07 (s,1H), 6.72 (d, J = 8.8 Hz, 2H), 6.69 (d, J = 8.8 Hz, 2H), 5.09 (brs, 1H,NH), 4.47 (d, J = 5.6 Hz, 2H), 3.67 (s, 3H), 3.48-3.50 (m, 4H),1.65-1.68 (m, 6H); LCMS (electrospray) m/z 360 (M + H)⁺.  70

White solid; mp = 222° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.38 (s, 1H,NH), 8.04 (d, J = 2.0 Hz, 1H), 7.79-7.82 (m, 3H), 7.69 (dd, J = 8.8 Hz,2.0 Hz, 1H), 6.93 (d, J = 8.8 Hz, 2H), 3.80 (s, 3H), 3.64-3.67 (m, 4H),1.70-1.73 (m, 6H); LCMS (electrospray) m/z 368 (M + H)⁺.  71

Green solid; mp = 127.5° C.; ¹H NMR (400 MHz, CDCl₃) δ 6.99 (s, 1H),6.90 (d, J = 8.8 Hz, 2H), 6.81 (d, J = 8.8 Hz, 2H), 5.11 (s, 2H), 3.76(s, 3H), 3.50-3.52 (m, 4H), 1.67- 1.69 (m, 6H); LCMS (electrospray) m/z361 (M + H)⁺.  72

Pale yellow solid; mp = 263.5° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.06 (s,1H), 8.11 (s, 1H), 7.58 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 8.8 Hz, 2H),3.74 (s, 3H), 3.69-3.72 (m, 4H), 2.09-2.19 (m, 4H); LCMS (electrospray)m/z 410 (M + H)⁺.  73

Pale pink solid; mp = 209.8° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.12 (s,1H), 8.08 (s, 1H), 7.62 (d, J = 8.8 Hz, 2H), 6.92 (d, J = 8.8 Hz, 2H),3.74 (s, 3H), 3.49-3.51 (m, 4H), 1.60-1.63 (m, 6H); LCMS (electrospray)m/z 374 (M + H)⁺.  74

¹H NMR (400 MHz, DMSO-d₆) δ 8.57 (s, 1H), 8.20-8.22 (m, 1H), 7.94 (brs,1H, NH), 7.70-7.74 (m, 1H), 7.57- 7.60 (m, 1H), 3.80-3.81 (m, 4H),3.69-3.70 (m, 4H); LCMS (electrospray) m/z 403 (M + H)⁺.  75

Pale yellow solid; mp = 212.0° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.62(brs, 1H, NH), 9.28 (s, 1H), 8.24 (s, 1H), 7.69 (d, J = 8.8 Hz, 2H),6.94 (d, J = 8.8 Hz, 2H), 3.80 (s, 3H); LCMS (electrospray) m/z 291 (M +H)⁺.  76

Pale yellow solid; mp = 216.3° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.31(brs, 1H, NH), 7.93 (s, 1H), 7.66 (d, J = 8.8 Hz, 2H), 6.90 (d, J = 8.8Hz, 2H), 3.86-3.96 (m, 3H), 3.78 (s, 3H), 3.40-3.46 (m, 2H), 1.94-1.99(m, 2H), 1.61-1.65 (m, 2H); LCMS (electrospray) m/z 399 (M + H)⁺.  77

Pale yellow solid; mp = 190.3° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.28(brs, 1H, NH), 7.93 (s, 1H), 7.66 (d, J = 8.4 Hz, 2H), 7.32-7.43 (m,4H), 7.25-7.31 (m, 1H), 6.90 (d, J = 8.4 Hz, 2H), 4.64 (s, 2H),3.80-3.90 (m, 3H), 3.78 (s, 3H), 3.48-3.57 (m, 2H), 2.10-2.18 (m, 2H),1.75-1.85 (m, 2H); LCMS (electrospray) m/z 480 (M + H)⁺.  78

Pale yellow solid; mp = 274.4° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.24(s, 1H), 7.92 (s, 1H), 7.66 (d, J = 8.4 Hz, 2H), 6.90 (d, J = 8.4 Hz,2H), 3.79 (s, 3H), 3.51-3.54 (m, 4H), 2.09-2.13 (m, 4H); LCMS(electrospray) m/z 359 (M + H)⁺.  79

Ivory solid; mp = 231° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 9.96 (s, 1H, NH),8.31 (brs, 1H, NH), 8.00 (s, 1H), 7.58 (d, J = 9.2 Hz, 2H), 6.92 (d, J =9.2 Hz, 2H), 3.75 (s, 3H), 3.61-3.65 (m, 1H), 1.94-1.99 (m, 2H),1.69-1.73 (m, 2H), 1.55-1.60 (m, 1H), 1.15-1.36 (m, 5H); LCMS(electrospray) m/z 387 (M + H)⁺.  80

Brown solid; mp = 256° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.02 (s, 1H,NH), 8.08 (s, 1H), 7.59 (d, J = 8.8 Hz, 2H), 6.92 (d, J = 8.8 Hz, 2H),4.09-4.15 (m, 4H), 3.73 (s, 3H), 2.43-2.46 (m, 2H); LCMS (electrospray)m/z 345 (M + H)⁺.  81

Ivory solid; mp = 157° C.; ¹H NMR (400 MHz, CDCl₃) δ 6.62 (s, 1H), 6.61(brs, 1H, NH), 3.45-3.49 (m, 4H), 1.66- 1.71 (m, 6H), 1.50 (s, 9H); LCMS(electrospray) m/z 339 (M + H)⁺.  82

Yellow solid; mp = 172.1° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.52 (s, 1H),6.82-6.87 (m, 4H), 6.30 (bbrt, 1H), 4.07 (t, J = 4.8 Hz, 2H), 3.80-3.86(m, 6H), 3.58-3.61 (m, 4H); LCMS (electrospray) m/z 420 (M + H)⁺.  83

Pale yellow solid; mp = 268.3° C.; ¹H NMR (400 MHz, CDCl₃ + MeOH-d₄) δ7.79 (s, 1H), 7.69-7.73 (m, 2H), 7.38 (d, J = 8.8 Hz, 1H), 3.76-3.78 (m,4H), 3.51-3.53 (m, 4H), 2.59 (s, 3H); LCMS (electrospray) m/z 401 (M +H)⁺.  84

Pale yellow solid; mp = 262.3° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.44 (s,1H), 8.51 (s, 1H), 8.22-8.27 (m, 1H), 8.15 (s, 1H), 7.19 (dd, J = 8.8,2.8 Hz, 1H), 3.72- 3.75 (m, 4H), 3.53-3.55 (m, 4H); LCMS (electrospray)m/z 365 (M + H)⁺.  85

Pale yellow solid; mp = 273.6° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.34 (s,1H), 8.13-8.16 (m, 2H), 7.58- 7.60 (m, 1H), 7.52-7.54 (m, 1H), 3.70-3.74(m, 4H), 3.51-3.54 (m, 4H), 2.58 (s, 3H); LCMS (electrospray) m/z 401(M + H)⁺.  86

White solid; mp = 272.2° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 10.47 (s, 1H),8.28 (s, 1H), 8.15 (s, 1H), 7.58-7.59 (m, 2H), 3.72-3.74 (m, 4H),3.52-3.54 (m, 4H), 2.58 (s, 3H).  87

Pale yellow solid; mp = 169.5° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.48(brs, 1H, NH), 7.97 (s, 1H), 7.53-7.55 (m, 2H), 7.38-7.42 (m, 2H),7.31-7.35 (m, 1H), 7.13- 7.17 (m, 1H), 7.05 (d, J = 8.8 Hz, 2H), 6.74(dd, J = 8.8, 2.2 Hz, 1H), 3.78-3.83 (m, 4H), 3.56-3.62 (m, 4H); LCMS(electrospray) m/z 438 (M + H)⁺.  88

Pale yellow solid; mp = 331.7° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.40(brs, 1H, NH), 8.42 (s, 1H), 8.30 (s, 1H), 8.19 (s, 1H), 8.05 (d, J =8.8 Hz, 1H), 7.83 (d, J = 8.8 Hz, 1H), 3.72-3.78 (m, 4H), 3.52-3.57 (m,4H), 1.66 (s, 9H); LCMS (electrospray) m/z 486 (M + H)⁺.  89

Pale yellow solid; mp = 329.8° C.; ¹H NMR (400 MHz, acetone-d₆) δ 12.20(brs, 1H, NH), 9.48 (brs, 1H, NH), 8.27 (s, 1H), 8.01-8.04 (m, 2H), 7.65(d, J = 8.0 Hz, 1H), 7.55 (d, J = 8.0 Hz, 1H), 3.78-3.84 (m, 4H), 3.57-3.62 (m, 4H); LCMS (electrospray) m/z 386 (M + H)⁺.  90

Pale yellow solid; mp = 239.3° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 9.97(brs, 1H, NH), 8.39 (brs, 1H, NH), 8.01 (s, 1H), 7.58 (d, J = 8.8 Hz,2H), 6.91 (d, J = 8.8 Hz, 2H), 4.04-4.14 (m, 1H), 3.74 (s, 3H),1.90-2.00 (m, 2H), 1.62-1.74 (m, 2H), 1.50-1.62 (m, 4H); LCMS(electrospray) m/z 374 (M + H)⁺.  91

Pale yellow solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.29 (s, 1H), 7.94 (s,1H), 7.66 (d, J = 8.8 Hz, 2H), 7.28 (d, J = 8.8 Hz, 2H), 6.90 (d, J =8.8 Hz, 4H), 3.79 (s, 6H), 3.59- 3.62 (m, 4H), 3.52 (s, 2H), 2.56-2.58(m, 4H); LCMS (electrospray) m/z 494 (M + H)⁺.  92

Pale yellow solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.32 (s, 1H), 7.96 (s,1H), 7.67 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 8.8 Hz, 2H), 3.79 (s, 3H),3.58-3.59 (m, 4H), 3.00-3.01 (m, 4H);; LCMS (electrospray) m/z 374 (M +H)⁺.  93

Pale yellow solid; mp = 249° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.29 (s,1H, NH), 7.94 (s, 1H), 7.67 (d, J = 9.2 Hz, 2H), 6.90 (d, J = 9.2 Hz,2H), 4.73-4.76 (m, 1H), 4.62-4.63 (m, 1H), 3.79 (s, 3H), 3.67-3.69 (m,1H), 3.44- 3.50 (m, 3H), 1.89-1.93 (m, 2H), 1.40-1.46 (m, 9H); LCMS(electrospray) m/z 487 (M + H)⁺.  94

Pale yellow solid; mp = 161° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.30 (s,1H, NH), 7.93 (s, 1H), 7.67 (d, J = 8.8 Hz, 2H), 6.90 (d, J = 8.8 Hz,2H), 4.73-4.75 (m, 1H), 4.40-4.44 (m, 1H), 3.78 (s, 3H), 3.49-3.62 (m,4H), 1.85- 1.96 (m, 2H); LCMS (electrospray) m/z 387 (M + H)⁺.  95

Yellow solid; mp = 169° C.; ¹H NMR (400 MHz, acetone- d₆) δ 9.28 (s, 1H,NH), 7.92 (s, 12H), 7.66 (d, J = 8.8 Hz, 2H), 7.26-7.37 (m, 5H), 6.90(d, J = 8.8 Hz, 2H), 4.61- 4.70 (m, 2H), 3.87-3.91 (m, 1H), 3.78 (s,3H), 3.56-3.70 (m, 4H), 2.02-2.05 (m, 2H), 1.77-1.79 (m, 1H), 1.63- 1.65(m, 1H); LCMS (electrospray) m/z 480 (M + H)⁺.  96

Beige solid; mp = 238° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.27 (s, 1H,NH), 7.92 (s, 1H), 7.66 (d, J = 8.4 Hz, 2H), 6.90 (d, J = 8.4 Hz, 2H),4.15 (d, J = 4.0 Hz, 1H, OH), 3.90- 3.94 (m, 1H), 3.73-3.83 (m, 5H),3.36-3.40 (m, 1H), 3.20-3.25 (m, 1H), 1.92-2.02 (m, 2H), 1.59-1.65 (m,2H); LCMS (electrospray) m/z 390 (M + H)⁺.  97

Yellow solid; mp = 246° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 9.91 (s, 1H,NH), 8.05 (s, 1H), 7.44 (d, J = 8.8 Hz, 2H), 6.72 (d, J = 8.8 Hz, 2H),3.51-3.55 (m, 4H), 1.60- 1.64 (m, 6H); LCMS (electrospray) m/z 359 (M +H)⁺.  98

Green solid; mp = 92° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 11.33 (s, 1H, NH),7.96 (d, J = 8.8 Hz, 2H), 7.08 (d, J = 8.8 Hz, 2H), 6.97 (s, 1H), 3.84(s, 3H), 3.41-3.44 (m, 4H), 1.59-1.63 (m, 6H); LCMS (electrospray) m/z373 (M + H)⁺.  99

Ivory solid; mp = 240° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.22 (s, 1H,NH), 8.13 (s, 1H), 7.68-7.72 (m, 2H), 7.16-7.20 (m, 2H), 3.72-3.74 (m,4H), 3.52-3.55 (m, 4H); LCMS (electrospray) m/z 363 (M + H)⁺. 100

Ivory solid; mp = 195° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.03 (s, 1H,NH), 8.09 (s, 1H), 7.59 (d, J = 8.3 Hz, 2H), 6.91 (d, J = 8.4 Hz, 2H),4.04-4.09 (m, 1H), 3.87-3.92 (m, 1H), 3.47-3.50 (m, 1H), 3.19-3.26 (m,1H), 3.00- 3.08 (m, 2H), 2.84-2.93 (m, 1H), 2.17-2.23 (m, 1H), 1.99-2.12(m, 2H), 1.81-1.89 (m, 1H), 1.68-1.75 (m, 2H), 1.34-1.42 (m, 1H),1.15-2.00 (m, 2H); LCMS (electrospray) m/z 414 (M + H)⁺. 101

Pale yellow solid; mp = 281.8° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.41 (s,1H), 8.67 (s, 1H), 8.27 (s, 1H), 8.19 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H),7.60-7.62 (m, 1H), 3.73- 3.75 (m, 4H), 3.53-3.55 (m, 4H); LCMS(electrospray) m/z 387 (M + H)⁺. 102

Pale yellow solid; mp = 209.3° C.; ¹H NMR (400 MHz, DMSO-d₆, ~30%mixture of conformational isomers) δ 10.22 (s, 1H), 8.25 & 8.27 (s, 1H),7.66 (d, J = 8.0 Hz, 1H), 7.45 (d, J = 8.0 Hz, 1H), 7.33 (dd, J = 8.0,8.0 Hz, 1H), 3.73-3.76 (m, 4H), 3.53-3.61 (m, 4H), 2.63 (s, 3H); LCMS(electrospray) m/z 401 (M + H)⁺. 103

White solid; mp = 319.1° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 10.46 (s, 1H),8.21 (s, 1H), 7.92-7.94 (m, 4H), 3.73- 3.75 (m, 4H), 3.53-3.56 (m, 4H),2.57 (s, 3H); LCMS (electrospray) m/z 428 (M + H)⁺. 104

White solid; mp = 230.9° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 9.99 (s, 1H),8.79 (brs, 1H), 8.18 (s, 1H), 8.02 (d, J = 1.6 Hz, 1H), 7.71 (d, J = 8.4Hz, 1H), 7.57-7.60 (m, 2H), 6.90-6.92 (m, 2H), 6.81 (dd, J = 8.4, 1.6Hz, 1H), 4.49 (d, J = 3.6 Hz, 2H), 3.83 (s, 3H), 3.74 (s, 3H); LCMS(electrospray) m/z 427 (M + H)⁺. 105

Pale yellow solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.66 (brs, 1H, NH),8.30-8.35 (m, 2H), 8.24 (s, 1H), 7.63- 7.71 (m, 1H), 3.78-3.83 (m, 4H),3.58-3.63 (m, 4H); LCMS (electrospray) m/z 365 (M + H)⁺. 106

Pale yellow solid; mp = 225.0° C.; ¹H NMR (400 MHz, DMSO-d₆) d 10.01(brs, 1H, NH), 8.08 (s, 1H), 7.57 (d, J = 8.0 Hz, 2H), 7.27-7.32 (m,2H), 7.00 (d, J = 8.0 Hz, 2H), 6.89-6.98 (m, 3H), 4.65-4.72 (m, 1H),3.78-3.87 (m, 2H), 3.72 (s, 3H), 3.48-3.57 (m, 2H), 2.02-2.11 (m, 2H),1.70-1.80 (m, 2H); LCMS (electrospray) m/z 466 (M + H)⁺. 107

Pale yellow solid; mp = 259.3° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.48(brs, 1H, NH), 8.21 (s, 1H), 7.94 (d, J = 7.6 Hz, 2H), 7.71 (d, J = 7.6Hz, 2H), 3.72-3.77 (m, 4H), 3.53-3.58 (m, 4H); LCMS (electrospray) m/z414 (M + H)⁺. 108

Pale yellow solid; mp = 274.0° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.44 (s,1H), 8.20 (s, 1H), 7.93 (d, J = 8.4 Hz, 2H), 7.85 (d, J = 8.4 Hz, 2H),4.28 (q, J = 6.8 Hz, 2H), 3.71-3.78 (m, 4H), 3.52-3.54 (m, 4H), 1.30 (t,J = 6.8 Hz, 3H); LCMS (electrospray) m/z 417 (M + H)⁺. 109

White solid; mp = 223.4° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 10.11 (s, 1H),8.13 (s, 1H), 7.43-7.47 (m, 2H) 7.36- 7.40 (m, 3H), 7.27-7.33 (m, 1H),7.20-7.25 (m, 2H), 6.72-6.74 (m, 1H), 5.08 (s, 2H), 3.71-3.72 (m, 4H),3.51- 3.52 (m, 4H); LCMS (electrospray) m/z 451 (M + H)⁺. 110

White solid; mp = 219.8° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 10.03 (s, 1H),8.11 (s, 1H), 7.63 (d, J = 8.8 Hz, 2H), 6.96 (d, J = 8.8 Hz, 2H),3.73-3.78 (m, 4H), 3.58 (s, 3H), 3.53 (s, 3H), 2.23-2.78 (s, 4H); LCMS(electrospray) m/z 388 (M + H)⁺. 111

Pale yellow solid; mp = 302.6° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.53 (s,1H), 8.24 (s, 1H), 8.12 (d, J = 8.0 Hz, 2H), 7.95 (d, J = 8.0 Hz, 2H),7.19 (d, J = 7.6 Hz, 2H), 6.99 (d, J = 7.6 Hz, 2H), 3.78 (s, 3H),3.73-3.74 (m, 4H), 3.54-3.55 (m, 4H); LCMS (electrospray) m/z 495 (M +H)⁺. 112

Pale yellow solid; mp = 212° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.78 (s,1H, NH), 8.05 (s, 1H), 7.99 (d, J = 7.6 Hz, 2H), 7.74 (d, J = 7.6 Hz,2H), 3.79-3.82 (m, 4H), 3.59-3.62 (m, 4H); LCMS (electrospray) m/z 371(M + H)⁺. 113

Yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 12.48 (s, 1H, NH), 10.25 (s,1H, NH), 8.15-8.25 (m, 2H), 7.50- 7.58 (m, 3H), 3.81-3.84 (m, 4H),3.61-3.63 (m, 4H); LCMS (electrospray) m/z 386 (M + H)⁺. 114

Orange solid; mp = 112° C.; ¹H NMR (400 MHz, acetone- d₆) δ 9.26 (s, 1H,NH), 7.93 (s, 1H), 7.67 (d, J = 6.8 Hz, 2H), 7.33 (d, J = 6.8 Hz, 2H),6.89-6.94 (m, 4H), 4.75 (s, 2H), 3.79 (s, 3H), 3.78 (s, 3H), 3.59 (q, J= 7.2 Hz, 2H), 1.23 (t, J = 7.2 Hz, 3H); LCMS (electrospray) m/z 454(M + H)⁺. 115

White solid; mp = 149° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.54 (s, 1H,NH), 8.15 (s, 1H), 7.69 (d, J = 8.8 Hz, 2H), 6.93 (d, J = 8.8 Hz, 2H),3.98 (s, 3H), 3.40-3.47 (m, 1H), 1.45 (d, J = 6.8 Hz, 6H); LCMS(electrospray) m/z 333 (M + H)⁺. 116

White solid; mp = 291° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.16 (s, 1H,NH), 8.13-8.14 (m, 2H), 8.01 (s, 1H), 7.51- 7.52 (m, 2H), 3.81 (s, 3H),3.69-3.73 (m, 4H), 3.48- 3.53 (m, 4H); LCMS (electrospray) m/z 400 (M +H)⁺. 117

White solid; mp = 314° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.25 (s, 1H,NH), 8.17 (s, 1H), 8.11 (s, 1H), 8.05 (d, J = 2.0 Hz, 1H), 7.58 (d, J =8.8 Hz, 1H), 7.39 (dd, J = 8.8 Hz, 2.0 Hz, 1H), 3.79 (s, 3H), 3.71-3.74(m, 4H), 3.51-3.54 (m, 4H); LCMS (electrospray) m/z 400 (M + H)⁺. 118

Orange solid; mp = 199° C.; ¹H NMR (400 MHz, acetone- d₆) δ 9.52 (s, 1H,NH), 8.11 (s, 1H), 8.01 (s, 1H), 7.71- 7.73 (m, 1H), 7.26-7.29 (m, 2H),3.78-3.81 (m, 4H), 3.57-3.60 (m, 4H); LCMS (electrospray) m/z 425 (M +H)⁺. 119

White solid; mp = 232° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 9.96 (s, 1H, NH),8.23 (brs, 1H, NH), 8.00 (s, 1H), 7.59 (d, J = 8.8 Hz, 2H), 6.91 (d, J =8.8 Hz, 2H), 3.73 (s, 3H), 3.61-3.64 (m, 1H), 1.94-1.99 (m, 2H),1.69-1.74 (m, 2H), 1.55-1.60 (m, 1H), 1.17-1.35 (m, 3H); LCMS(electrospray) m/z 389 (M + H)⁺. 120

Pale yellow solid; ¹H NMR (400 MHz, MeOH-d₄) δ 7.87 (s, 1H), 7.85 (d, J= 8.8 Hz, 2H), 6.91 (d, J = 8.8 Hz, 2H), 4.10 (m, 2H), 3.79 (s, 3H),3.14-3.22 (m, 3H), 1.86-1.89 (m, 2H), 1.78-1.79 (m, 1H), 1.33-1.39 (m,3H); LCMS (electrospray) m/z 403 (M + H)⁺. 121

Ivory solid; mp = 131° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.27 (s, 1H,NH), 7.91 (s, 1H), 7.65 (d, J = 8.8 Hz, 2H), 7.32 (d, J = 8.8 Hz, 2H),6.89-6.92 (m, 4H), 4.71 (s, 2H), 4.49-4.53 (m, 1H), 3.78 (s, 6H), 1.31(d, J = 6.8 Hz, 6H); LCMS (electrospray) m/z 468 (M + H)⁺. 122

Pale yellow solid; mp = 238.5° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.23 (s,1H), 8.13 (s, 1H), 8.05 (s, 1H), 7.60- 7.63 (m, 2H), 4.85 (d, J = 4.0Hz, 1H), 3.79-3.82 (m, 3H), 3.36-3.39 (m, 2H), 2.60 (s, 3H), 1.84-1.87(m, 2H), 1.46-1.51 (m, 2H); LCMS (electrospray) m/z 415 (M + H)⁺. 123

Pale yellow solid; mp = 334.4° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.41 (s,1H), 8.16 (s, 1H), 7.92-7.94 (m, 4H), 4.84 (brs, 1H), 3.75-3.78 (m, 3H),3.34-3.36 (m, 2H), 2.55 (s, 3H), 1.80-1.83 (m, 2H), 1.46-1.49 (m, 2H);LCMS (electrospray) m/z 442 (M + H)⁺. 124

Yellow solid; mp = 237.9° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 10.23 (s,1H), 8.13 (s, 1H), 8.05 (s, 1H), 7.60-7.63 (m, 2H), 3.72-3.78 (m, 2H),3.37-3.51 (m, 3H), 3.29 (s, 3H), 2.59 (s, 3), 1.92-1.97 (m, 2H),1.55-1.60 (m, 2H); LCMS (electrospray) m/z 429 (M + H)⁺. 125

Ivory solid; mp = 268° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.01 (s, 1H,NH), 8.07 (s, 1H), 7.58 (d, J = 8.8 Hz, 2H), 6.90 (d, J = 8.8 Hz, 2H),3.96-3.99 (m, 2H), 3.72 (s, 3H), 3.54-3.57 (m, 6H), 3.41-3.44 (m, 2H),3.21-3.27 (m, 2H), 2.93-2.99 (m, 1H), 1.73-1.76 (m, 2H), 1.58-1.67 (m,2H); LCMS (electrospray) m/z 487 (M + H)⁺. 126

White solid; mp = 276.1° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 9.99 (s, 1H),8.07 (s, 1H), 7.457 (d, J = 8.8 Hz, 2H), 7.32 (s, 1H), 6.90 (d, J = 8.8Hz, 2H), 6.83 (s, 1H), 3.94- 3.98 (m, 2H), 3.72 (s, 3H), 3.14-3.18 (m,3H), 1.80-1.83 (m, 2H), 1.57-1.61 (m, 2H); LCMS (electrospray) m/z 416(M + H)⁺. 127

White solid; mp = 273.4° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 10.01 (s, 1H),8.07 (s, 1H), 7.57 (d, J = 8.8 Hz, 2H), 6.90 (d, J = 8.8 Hz, 2H),3.96-3.99 (m, 2H), 3.72 (s, 3H), 3.05 (s, 3H), 2.87-2.99 (m, 2H), 2.80(s, 3H), 1.73-1.76 (m, 2H), 1.57-1.63 (m, 3H); LCMS (electrospray) m/z444 (M + H)⁺. 128

Ivory solid; mp = 354° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.48 (s, 1H),8.25 (s, 1H), 7.86-7.;93 (m, 4H), 3.76- 3.79 (m, 4H), 3.57-3.59 (m, 4H),1.58 (s, 9H); LCMS (electrospray) m/z 426 (M + H)⁺. 129

Pale yellow solid; mp = 244° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.00 (s,1H), 8.14 (s, 1H), 7.66-7.68 (m, 2H), 6.93-6.95 (m, 2H), 5.16 (s, 1H),4.50-4.51 (m, 1H), 3.78 (s, 3H), 3.38-3.66 (m, 4H), 2.01-2.16 (m, 2H).130

¹H NMR (400 MHz, DMSO-d₆) δ 10.00 (s, 1H), 8.14 (s, 1H), 7.66-7.68 (m,2H), 6.93-6.95 (m, 2H), 5.16 (s, 1H), 4.50-4.51 (m, 1H), 3.78 (s, 3H),3.38-3.66 (m, 4H), 2.01-2.16 (m, 2H). 131

White solid; mp = 288.0° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 10.12 (brs,1H, NH), 8.28 (s, 1H), 8.15 (s, 1H), 8.11 (s, 1H), 7.57 (d, J = 9.2 Hz,1H), 7.43 (d, J = 9.2 Hz, 1H), 4.14 (s, 3H), 3.72-3.77 (m, 4H),3.52-3.56 (m, 4H); LCMS (electrospray) m/z 400 (M + H)⁺. 132

White solid; mp = 313.7° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 10.22 (brs,1H, NH), 8.15 (s, 1H), 8.13 (s, 1H), 8.02 (s, 1H), 7.61-7.63 (m, 2H),4.03 (s, 3H), 3.72-3.76 (m, 4H), 3.52-3.56 (m, 4H); LCMS (electrospray)m/z 400 (M + H)⁺. 133

White solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.77 (brs, 1H, NH), 8.04 (s,1H), 7.99 (d, J = 8.8 Hz, 2H), 7.73 (d, J = 8.8 Hz, 2H), 3.88-3.99 (m,3H), 3.43-3.49 (m, 2H), 1.92-2.02 (m, 2H), 1.59-1.69 (m, 2H); LCMS(electrospray) m/z 385 (M + H)⁺. 134

White solid; mp = 241.7° C.; ¹H NMR (400 MHz, acetone- d₆) δ 9.46 (brs,1H, NH), 7.96 (s, 1H), 7.74-7.82 (m, 2H), 7.07-7.14 (m, 2H), 3.94-4.02(m, 1H), 3.83-3.93 (m, 2H), 3.40-3.49 (m, 2H), 1.92-2.02 (m, 2H),1.56-1.59 (m, 2H); LCMS (electrospray) m/z 378 (M + H)⁺. 135

Yellow solid; mp = 231.3° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 10.14 (s,1H), 8.15 (s, 1H), 7.89 (s, 1H), 7.44 (s, 2H), 6.57 (s, 1H), 3.73-3.75(m, 4H), 3.52-3.55 (m, 4H), 2.43 (s, 3); LCMS (electrospray) m/z 400(M + H)⁺. 136

White solid; mp = 296.2° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 10.19 (s, 1H),8.12 (s, 1H), 7.72 (d, J = 8.8 Hz, 2H), 7.18 (d, J = 8.8 Hz, 2H),3.98-4.01 (m, 2H), 3.06 (s, 3H), 2.96-3.01 (m, 2H), 2.82 (s, 3H),1.75-1.78 (m, 2H), 1.59- 1.62 (m, 3H); LCMS (electrospray) m/z 432 (M +H)⁺. 137

Pale yellow solid; mp = 295.9° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.43 (s,1H), 8.51 (s, 1H), 8.23-8.27 (m, 1H), 8.13 (s, 1H), 7.18-7.21 (m, 1H),3.99-4.02 (m, 2H), 3.11 (s, 3H), 2.96-3.06 (m, 2H), 2.89 (s, 3H), 1.75-1.79 (m, 2H), 1.57-1.65 (m, 3H); LCMS (electrospray) m/z 433 (M + H)⁺.138

White solid; mp = 284.2° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 10.25 (s, 1H),8.15 (s, 1H), 8.05 (s, 1H), 7.60-7.61 (m, 2H), 3.99-4.02 (m, 2H), 3.06(s, 3H), 2.97-2.99 (m. 2H), 2.82 (s, 3H), 2.60 (s, 3H), 1.75-1.78 (m,2H), 1.59- 1.63 (m, 3H); LCMS (electrospray) m/z 469 (M + H)⁺. 139

Pale yellow solid; mp = 247.5° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 9.73 (s,1H), 7.67 (s, 1H), 7.26 (d, J = 8.4 Hz, 2H), 6.73 (d, J = 8.4 Hz, 2H),3.00-3.01 (m, 4H), 2.35- 2.36 (m, 4H); LCMS (electrospray) m/z 362 (M +H)⁺. 140

Pale yellow solid; mp = 235.3° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 9.79 (s,1H), 7.69 (s, 1H), 7.60 (s, 1H), 7.15- 7.16 (m, 2H), 2.88-3.03 (m, 4H),2.35-2.38 (m, 4H), 2.15 (s, 3H); LCMS (electrospray) m/z 399 (M + H)⁺.141

Pale yellow solid; mp = 277.0° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.10 (s,1H), 8.14 (s, 1H), 8.00 (s, 1H), 7.81 (s, 1H),l 3.73-3.75 (m, 4H),3.53-3.55 (m, 4H), 2.63 (s, 3H); LCMS (electrospray) m/z 435 (M + H)⁺.142

Pale yellow solid; mp = 246.3° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.17(brs, 1H, NH), 8.11 (s, 1H), 7.69-7.75 (m, 2H), 7.16-7.20 (m, 2H), 6.55(brs, 1H OH), 4.52- 4.58 (m, 1H), 3.98-4.01 (m, 2H), 3.42 (s, 2H),3.13-3.22 (m, 2H), 1.68-1.80 (m, 2H), 1.22-1.24 (m, 2H); LCMS(electrospray) m/z 392 (M + H)⁺. 143

Pale yellow solid; mp = 240.8° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.77(brs, 1H, NH), 8.52 (s, 1H), 8.32-8.38 (m, 1H), 8.00 (s, 1H), 7.06-7.08(m, 1H), 4.09-4.12 (m, 2H), 3.78-4.82 (m, 1H), 3.46 (s, 2H), 3.16-3.23(m, 2H), 1.80-1.90 (m, 2H), 1.30-1.40 (m, 2H); LCMS (electrospray) m/z393 (M + H)⁺. 144

White solid; mp = 196.4° C.; ¹H NMR (400 MHz, acetone- d₆) δ 9.61 (brs,1H, NH), 8.13 (s, 1H), 8.00 (s, 1H), 7.65 (d, J = 9.2 Hz, 1H), 7.49 (d,J = 9.2 Hz, 1H), 4.08-4.11 (m, 2H), 3.80-4.90 (m, 1H), 3.46 (s, 2H),3.15-3.21 (m, 2H), 2.59 (s, 3H), 1.79-1.90 (m, 2H), 1.28-1.39 (m, 2H);LCMS (electrospray) m/z 429 (M + H)⁺. 145

Ivory solid; mp = 314° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.21 (s, 1H,NH), 8.17 (s, 1H), 7.69-7.75 (m, 5H), 6.64 (s, 1H), 3.87 (s, 3H),3.72-3.76 (m, 4H), 3.52-3.56 (m, 4H); LCMS (electrospray) m/z 425 (M +H)⁺. 146

White solid; mp = 225° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.22 (s, 1H,NH), 8.15 (s, 1H), 7.75 (d, J = 8.0 Hz, 2H), 7.41 (d, J = 8.0 Hz, 2H),7.05 (d, J = 8.0 Hz, 2H), 7.02 (d, J = 8.0 Hz, 2H), 3.72-3.76 (m, 4H),3.52-3.55 (m, 4H); LCMS (electrospray) m/z 472 (M + H)⁺. 147

Pale yellow solid; mp = 275.3° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.08 (s,1H), 8.14 (s, 1H), 7.92 (s, 1H), 7.87 (s, 1H), 3.71-3.73 (m, 4H),3.51-3.353 (m, 4H), 2.61 (s, 3H); LCMS (electrospray) m/z 435 (M + H)⁺.148

Yellow solid; mp = 248° C.; ¹H NMR (400 MHz, acetone- d₆) δ 9.85 (s, 1H,NH), 8.21 (s, 1H), 8.10 (s, 1H), 7.89-7.95 (m, 2H), 3.79-3.81 (m, 4H),3.58-3.61 (m, 4H), 2.59 (s, 3H); LCMS (electrospray) m/z 462 (M + H)⁺.149

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.04 (s, 1H), 8.09 (s,1H), 7.59 (d, J = 8.0 Hz, 2H), 6.92 (d, J = 8.0 Hz, 2H), 3.89-3.92 (m,2H), 3.74 (s, 3H), 1.93-1.96 (m, 3H), 1.61-1.64 (m, 2H), 1.19-1.23 (m,2H); LCMS (electrospray) m/z 417 (M + H)⁺. 150

Pale yellow solid; mp = 244.0° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 9.93 (s,1H), 8.11 (s, 1H), 7.57 (s, 1H), 7.53 (s, 1H), 3.73-3.75 (m, 4H),3.52-3.54 (m, 4H), 2.67 (q, J = 7.2 Hz, 2H), 2.60 (s, 3H), 1.14 (t, J =7.2 Hz, 3H); LCMS (electrospray) m/z 429 (M + H)⁺. 151

Ivory solid; mp = 176° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.52 (s, 1H,NH), 8.14 (s, 1H), 8.00 (s, 1H), 7.63-7.66 (m, 1H), 7.51 (d, J = 8.8 Hz,1H), 3.75-3.99 (m, 4H), 3.45-3.73 (m, 3H), 2.58 (s, 3H), 1.82-2.02 (m,2H), 0.99 (t, J = 7.6 Hz, 3H); LCMS (electrospray) m/z 429 (M + H)⁺. 152

Ivory solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.28 (s, 1H, NH), 8.17 (s,1H), 8.04 (s, 1H), 7.57-7.60 (m, 2H), 4.88 (s, 1H, OH), 3.89-3.97 (m,2H), 3.77-3.80 (m, 1H), 3.50-3.68 (m, 3H), 3.41-3.44 (m, 1H), 3.15-3.20(m, 1H), 2.98=-3.04 (m, 1H), 2.59 (s, 3H); LCMS (electrospray) m/z 431(M + H)⁺. 153

White solid; mp = 214° C.; ¹H NMR (400 MHz, acetone-d₆) δ 9.54 (s, 1H,NH), 8.14 (s, 1H), 8.01 (d, J = 2.0 Hz, 1H), 7.65 (dd, J = 8.8 Hz, 2.0Hz, 1H), 7.51 (d, J = 8.8 Hz, 1H), 4.00-4.03 (m, 1H), 3.91-3.94 (m, 1H),3.82-3.85 (m, 1H), 3.66-3.72 (m, 1H), 3.47-3.51 (m, 1H), 3.24-3.31 (m,1H), 2.92-2.98 (m, 1H, 2.49 (s, 3H), 1.56-1.61 (m, 2H), 1.00 (t, J = 7.6Hz, 3H); LCMS (electrospray) m/z 429 (M + H)⁺. 154

Pale yellow solid; mp = 287.3° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.38 (s,1H), 7.85-7.92 (m, 4H), 6.56 (s, 1H), 3.73-3.76 (m, 4H), 3.54-3.56 (m,4H), 2.38 (s, 3H); LCMS (electrospray) m/z 426 (M + H)⁺ 426. 155

Ivory solid; mp = 293° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.29 (s, 1H,NH), 8.17 (s, 1H), 7.91 (d, J = 2.8 Hz, 1H), 7.74-7.80 (m, 4H), 6.73 (d,J = 2.8 Hz, 1H), 5.40-5.43 (m, 1H), 3.92-3.97 (m, 1H), 3.67-3.75 (m,4H), 3.58- 3.66 (m, 1H), 3.54-3.58 (m, 4H), 2.11-2.15 (m, 1H), 1.92-1.98(m, 2H), 1.61-1.68 (m, 1H), 1.54-1.57 (m, 2H); LCMS (electrospray) m/z496 (M + H)⁺. 156

White solid; mp = 319° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 12.85 (brs, 1H,NH), 10.23 (s, 1H, NH), 8.17 (s, 1H), 7.76 (s, 4H), 7.68 (d, J = 2.0 Hz,1H), 6.66 (d, J = 2.0 Hz, 1H), 3.72-3.76 (m, 4H), 3.51-3.56 (m, 4H);LCMS (electrospray) m/z 411 (M + H)⁺. 157

Ivory solid; mp = 269° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.13 (s, 1H,NH), 8.00 (s, 1H), 7.64 (d, J = 8.8 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H),3.72-3.76 (m, 4H), 3.54-3.58 (m, 4H), 2.60 (s, 3H); LCMS (electrospray)m/z 478 (M + H)⁺. 158

Pale yellow solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.59 (s, 1H), 8.02 (d,J = 1.6 Hz, 1H), 7.90-7.92 (m, 2H), 7.50 (dd, J = 4.8, 1.6 Hz, 1H), 7.37(d, J = 7.6 Hz, 2H), 6.99 (d, J = 7.6 Hz, 2H), 6.82-6.84 (m, 2H), 5.27(s, 2H), 3.79- 3.82 (m, 4H), 3.75 (s, 3H), 3.58-3.61 (m, 4H); LCMS(electrospray) m/z 550 (M + H)⁺. 159

White solid; mp = 287.2° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 10.26 (s, 1H),8.16 (s, 1H), 7.78-7.80 (m, 3H), 7.68 (d, J = 8.8 Hz, 2H), 3.71-3.73 (m,4H), 3.51-3.53 (m, 4H); LCMS (electrospray) m/z 430 (M + H)⁺. 160

Pale yellow solid; mp = 305° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 12.92 (s,1H, NH), 10.89 (s, 1H, NH), 8.23 (s, 1H), 7.72-7.73 (m, 2H), 7.33-7.46(m, 3H), 6.94 (s, 1H), 3.71-3.73 (m, 4H), 3.51-3.53 (m, 4H); LCMS(electrospray) m/z 412 (M + H)⁺. 161

Pale yellow solid; mp = 292° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.29 (s,1H, NH), 8.74 (d, J = 2.4 Hz, 1H), 8.18 (s, 1H), 7.94 (dd, J = 8.0 Hz,2.4 Hz, 1H), 7.82 (d, J = 8.4 Hz, 2H), 7.68 (d, J = 8.4 Hz, 2H), 7.31(d, J = 8.0 Hz, 1H), 3.71-3.74 (m, 4H), 3.51-3.54 (m, 4H), 3.15 (s, 3H);LCMS (electrospray) m/z 437 (M + H)⁺. 162

Bright yellow solid; mp = 280.5° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.26(s, 1H), 8.18 (s, 1H), 7.92 (d, J = 4.8 Hz, 1H), 7.78 (d, J = 8.8 Hz,2H), 7.69 (d, J = 8.8 Hz, 2H), 3.81 (s, 3H), 3.73-3.75 (m, 4H),3.53-3.55 (m, 4H); LCMS (electrospray) m/z 444 (M + H)⁺. 163

Ivory solid; mp = 226° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 9.91 (s, 1H, NH),7.97 (s, 1H), 7.59 (d, J = 8.8 Hz, 1H), 7.54 (d, J = 8.8 Hz, 1H),3.71-3.74 (m, 4H), 3.50-3.53 (m, 4H), 2.58 (s, 3H), 2.54 (s, 3H); LCMS(electrospray) m/z 415 (M + H)⁺. 164

Yellow solid; mp = 361.2° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 10.22 (s,1H), 8.17 (s, 1H), 7.75-7.67 (m, 4H), 5.88 (s, 1H), 5.07 (t, J = 8.0 Hz,2H), 4.29 (t, J = 8.0 Hz, 2H), 3.76-3.71 (m, 4H), 3.56-3.51 (m, 4H);LCMS (electrospray) m/z 454 (M + H)⁺. 165

Pale yellow solid; mp = 257.8° C.; ¹H NMR (400 MHz, acetone-d₆) δ 10.01(brs, 1H, NH), 8.25 (d, J = 1.6 Hz, 1H), 8.22 (s, 1H), 7.77-7.79 (m,2H), 7.47-7.50 (m, 2H), 7.27-7.29 (m, 1H), 7.00 (d, J = 1.6 Hz, 1H),3.80- 3.82 (m, 4H), 3.59-3.61 (m, 4H); LCMS (electrospray) m/z 412 (M +H)⁺. 166

Ivory solid; mp = 285° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.57-7.62 (m, 5H),7.34 (brs, 1H, NH), 7.33 (d, J = 2.0 Hz, 1H), 7.30 (d, J = 8.8 Hz, 1H),7.22 (dd, J = 8.8, 2.0 Hz, 1H), 3.80-3.84 (m, 4H), 3.55-3.59 (m, 4H),2.59 (s, 3H); LCMS (electrospray) m/z 476 (M + H)⁺. 167

Ivory solid; mp = 245° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.19 (s, 1H,NH), 8.16 (s, 1H), 7.84 & 7.54 (s, 1H), 7.70- 7.74 (m, 2H), 7.35-7.40(m, 2H), 3.77 (s, 3H), 3.71- 3.75 (m, 4H), 3.51-3.55 (m, 4H), 2.36 (s,3H); LCMS (electrospray) m/z 440 (M + H)⁺. 168

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.02 (s, 1H), 8.10 (s,1H), 7.58 (d, J = 8.8 Hz, 2H), 7.20 (d, J = 8.8 Hz, 1H), 6.90 (d, J =8.8 Hz, 2H), 6.80 (d, J = 8.8 Hz, 2H), 4.65 (s, 2H), 3.72-3.77 (m, 2H),3.72 (s, 6H), 2.94- 2.97 (m, 2H); LCMS (electrospray) m/z 451 (M + H)⁺.169

White solid; mp = 247.5° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 10.26 (s, 1H),8.15 (s, 1H), 8.03 (s, 1H), 7.59-7.62 (m, 2H), 4.23-4.45 (m, 1H),3.93-3.96 (m, 2H), 3.73- 3.82 (m, 4H), 3.03 (s, 3H), 2.83 (s, 3H), 2.58(s, 3H); LCMS (electrospray) m/z 471 (M + H)⁺. 170

White solid; mp = 239° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.79 (d, J = 1.6Hz, 1H), 7.48 (dd, J = 8.8, 1.6 Hz, 1H), 7.46 (brs, 1, NH), 7.39 (d, J =8.8 Hz, 1H), 3.77-3.82 (m, 4H), 3.38-3.42 (m, 4H), 2.91-3.07 (m, 1H),2.86- 2.92 (m, 1H), 2.6-2.80 (m, 3H), 2.62 (s, 3H), 2.20-2.25 (m, 1H),2.02-2.11 (m, 1H); LCMS (electrospray) m/z 399 (M + H)⁺. 171

Ivory solid; mp = 323° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.33 (s, 1H,NH), 8.24-8.29 (m, 2H), 8.20 (d, J = 2.0 Hz, 1H), 8.16 (s, 1H), 7.77 (d,J = 8.8 Hz, 1H), 7.69 (dd, J = 8.8 2.0 Hz, 1H), 7.44-7.48 (m, 23H),3.97-4.03 (m, 2H), 3.21-3.24 (m, 2H), 3.06 (s, 3H), 2.95-3.01 (m, 1H),2.82 (s, 3H), 1.74-1.79 (m, 2H), 1.60-1.66 (m, 2H); LCMS (electrospray)m/z 549 (M + H)⁺. 172

Ivory solid; mp = 269° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.95 (s, 1H, NH),7.88 (d, J = 2.0 Hz, 1H), 7.56 (dd, J = 8.8, 2.0 Hz, 1H), 7.40 (d, J =8.8 Hz, 1H), 4.23 (s, 3H), 3.81-3.86 (m, 4H), 3.56-3.61 (m, 4H), 2.62(s, 3H); LCMS (electrospray) m/z 430 (M + H)⁺. 173

Ivory solid; mp = 167.2° C.; ¹H NMR (400 MHz, acetone- d₆) δ 7.50 (s,1H), 7.30-7.33 (m, 2H), 7.23-7.26 (m, 2H), 4.42-4.45 (m, 2H), 3.77-3.80(m, 4H), 3.53-3.56 (m, 4H), 2.93-2.99 (m, 2H), 2.60 (d, J = 7.2 Hz, 2H),1.92- 1.87 (m, 1H), 1.70-1.72 (m, 2H), 1.25-1.32 (m, 2H); LCMS(electrospray) m/z 462 (M + H)⁺. 174

Pale yellow solid; mp = 223.5° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.29(brs, 1H, NH), 8.19 (s, 1H), 8.05 (s, 1H), 7.61-7.64 (m, 2H), 7.35-7.48(m, 5H), 4.67-4.70 (m, 1H), 4.11-4.15 (m, 1H), 4.00-4.04 (m, 1H), 3.80-3.90 (m, 2H), 3.17-3.23 (m, 2H), 2.60 (s, 3H); LCMS (electrospray) m/z477 (M + H)⁺. 175

Pale yellow solid; mp = 288.6° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.30(brs, 1H, NH), 8.17 (s, 1H), 8.05 (s, 1H), 7.60-7.63 (m, 2H), 5.13-5.14(m, 1H), 4.14-4.17 (m, 1H), 3.92-4.00 (m, 2H), 3.82-3.86 (m, 1H), 3.62-3.63 (m, 1H), 3.46-3.50 (m, 1H), 3.10 (s, 3H), 2.84 (s, 3H), 2.60 (s,3H); LCMS (electrospray) m/z 472 (M + H)⁺. 176

Pale yellow solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.80 (brs, 1H, NH),8.23-8.25 (m, 1H), 8.17-8.20 (m, 1H), 8.09 (s, 1H), 7.73-7.76 (m, 1H0,7.55 (d, J = 8.8 Hz, 1H), 7.09 (d, J = 8.8 Hz, 1H), 3.77-3.79 (m, 4H),3.59- 3.61 (m, 4H), 2.60 (s, 3H); LCMS (electrospray) m/z 395 (M + H)⁺.177

Gray solid; mp = 219.4° C.; ¹H NMR (400 MHz, acetone- d₆) δ 7.72 (s,1H), 7.69 (brs, 1H), 7.50 (brs, 1H), 7.46 (d, J = 8.0 Hz, 1H), 7.23 (dd,J = 8.4, 1.6 Hz, 1H), 3.76-3.82 (m, 4H), 3.63 (q, J = 6.8 Hz, 2H),3.52-3.47 (m, 4H), 3.01 (t, J = 7.6 Hz, 2H), 2.56 (s, 3H); LCMS(electrospray) m/z 429 (M + H)⁺. 178

Yellow solid; mp = 133.6° C.; ¹H NMR (400 MHz, acetone- d₆) δ 9.50 (s,1H), 8.14 (s, 1H), 7.99 (s, 1H), 7.64 (dd, J = 8.8, 2.0 Hz, 1H), 7.50(d, J = 8.8 Hz, 1H), 4.01-4.12 (m, 2H), 3.19-3.34 (m, 2H), 3.14 (s, 3H),2.98-3.04 (m, 1H), 2.82 (s, 3H), 2.59 (s, 3H), 1.98-2.03 (m, 1H),1.80-1.87 (m, 1H), 1.69-1.78 (m, 2H); LCMS (electrospray) m/z 470 (M +H)⁺. 179

Pale brown solid; mp = 117.2° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.90 (d, J =2.0 Hz, 1H), 7.86 (s, 1H), 7.65 (s, 1H), 7.52 (dd, J = 8.8, 2.0 Hz, 1H),7.40 (d, J = 8.8 Hz, 1H), 5.25 (s, 2H), 3.84-3.87 (m, 4H), 3.43 (s, 3H),3.37- 3.42 (m, 4H), 2.63 (s, 3H); LCMS (electrospray) m/z 428 (M + H)⁺.180

White solid; mp = 274° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.27 (s, 1H,NH), 8.17 (s, 1H), 8.06 (s, 1H), 7.60-7.62 (m, 2H), 3.84-3.87 (m, 2H),3.70-3.72 (m, 2H), 2.81- 2.87 (m, 2H), 2.60 (s, 3H), 1.17 (d, J = 5.6Hz, 6H); LCMS (electrospray) m/z 429 (M + H)⁺. 181

Pale yellow solid; mp = 287° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.12 (s,1H, NH), 8.13 (s, 1H), 7.76-7.80 (m, 2H), 3.71-3.74 (m, 4H), 3.51-3.54(m, 4H), 2.59 (s, 3H); LCMS (electrospray) m/z 419 (M + H)⁺. 182

Ivory solid; mp = 266° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.33 (s, 1H),8.19 (s, 1H), 8.16 (s, 1H), 7.82 (d, J = 8.8 Hz, 2H), 7.68-7.69 (m, 1H),7.61 (d, J = 8.8 Hz, 2H), 7.07- 7.08 (m, 1H), 3.71-3.74 (m, 4H),3.51-3.54 (m, 4H); LCMS (electrospray) m/z 412 (M + H)⁺. 183

Pale yellow solid; mp = 246° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 9.96 (s,1H), 8.09 (s, 1H), 7.50 (d, J = 9.2 Hz, 2H), 7.22 (dd, J = 8.8 Hz, 5.6Hz, 2H), 7.10 (dd, J = 8.8 Hz, 8.8 Hz, 2H), 6.89 (d, J = 9.2 Hz, 2H),3.73-3.75 (m, 4H), 3.60-3.63 (m, 2H), 3.51-3.53 (m, 4H), 3.36-3.38 (m,1H), 2.54-2.59 (m, 3H), 1.61-1.64 (m, 3), 1.26- 1.31 (m, 2H); LCMS(electrospray) m/z 537 (M + H)⁺. 184

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.42 (s, 1H), 8.18 (s,1H), 7.91-7.95 (m, 4H), 3.97-4.01 (m, 2H), 3.05 (s, 3H), 2.94-3.00 (m,2H), 2.80 (s, 3H), 2.55 (s, 3H), 1.74-1.77 (m, 2H), 1.55-1.65 (m, 3H);LCMS (electrospray) m/z 496 (M + H)⁺. 185

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 9.29 (s, 1H), 7.82 (s,1H), 7.54-7.58 (m, 3H), 7.40-7.45 (m, 3H), 7.24-7.26 (m, 1H), 5.53 (s,2H), 3.71-3.74 (m, 4H), 3.53-3.55 (m, 4H), 2.57 (s, 3H); LCMS(electrospray) m/z 506 (M + H)⁺. 186

Pale yellow solid; mp = 264.9° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.23 (s,1H), 8.38-8.41 (m, 1H), 8.14 (s, 1H), 8.04 (s, 1H), 7.56-7.59 (m, 2H),7.28-7.32 (m, 2H), 7.21-7.23 (m, 3H), 4.25-4.27 (m, 2H), 3.98-4.02 (m,2H), 3.18-3.24 (m, 2H), 2.58 (s, 3H), 1.84-1.87 (m, 2H), 1.63-1.72 (m,3H); LCMS (electrospray) m/z 531 (M + H)⁺. 187

Ivory solid; mp = 104° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.58 (d, J = 2.0Hz, 1H), 7.37 (d, J = 8.8 Hz, 1H), 7.32 (dd, J = 8.8, 2.0 Hz, 1H), 6.48(s, 1H), 4.58 (s, 2H), 3.77-3.82 (m, 6H), 3.40-3.44 (m, 4H), 2.76-2.81(m, 2H), 2.61 (s, 3H); LCMS (electrospray) m/z 399 (M + H)⁺. 188

Ivory solid; mp = 248° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.48 (s, 1H),8.22 (s, 1H), 7.96 (d, J = 8.8 Hz, 2H), 7.86 (d, J = 8.8 Hz, 2H), 3.71(m, 4H), 3.52-3.56 (m, 4H), 2.54 (s, 3H); LCMS (electrospray) m/z 387(M + H)⁺. 189

Ivory solid; mp = 311° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.12 (s, 1H),8.42 (s, 1H), 8.20 (d, J = 2.0 Hz, 1H), 7.76 (dd, J = 8.8 Hz, 1H), 7.59(d, J = 8.8 Hz, 1H), 3.72-3.76 (m, 4H), 3.46-3.50 (m, 4H), 2.59 (s, 3H);LCMS (electrospray) m/z 384 (M + H)⁺. 190

Pale yellow solid; mp = 281.1° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 9.98(brs, 1H), 7.52 (d, J = 9.2 Hz, 2H), 7.29-7.35 (m, 4H), 6.95 (d, J = 9.2Hz, 2H), 3.71-3.73 (m, 4H), 3.58-3.60 (m, 1H), 3.50-3.52 (m, 4H),2.66-2.74 (m, 4H), 1.81-1.89 (m, 2H), 1.70-1.80 (m, 2H); LCMS(electrospray) m/z 539, 541 (M + H)⁺ (Cl⁻ isotope pattern). 191

White solid; mp = 171.7° C.; ¹H NMR (400 MHz, acetone- d₆) δ 8.10 (s,1H), 7.88 (d, J = 2.0 Hz, 1H), 7.44-7.37 (m, 2H), 5.90 (s, 1H),4.49-4.47 (m, 2H), 3.84 (t, J = 5.6 Hz, 2H), 3.72-3.76 (m, 4H),3.00-3.04 (m, 4H), 2.71-2.76 (m, 2H), 2.55 (s, 3H); LCMS (electrospray)m/z 399 (M + H)⁺. 192

Ivory solid; mp = 274.0° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 10.23 (s, 1H),8.14 (s, 1H), 8.04 (s, 1H), 7.56-7.63 (m, 2H), 3.59-3.70 (m, 3H),3.50-3.57 (m, 2H), 3.07 (s, 3H), 2.85 (s, 3H), 2.60 (s, 3H), 2.28-2.34(m, 1H0, 2.08- 2.14 (m, 1H); LCMS (electrospray) m/z 456 (M + H)⁺. 193

Pale yellow solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.98 (s, 1H), 8.10 (s,1H), 7.53 (d, J = 8.8 Hz, 2H), 7.32 (d, J = 8.8 Hz, 2H), 7.02 (d, J =8.8 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H), 4.54-4.55 (m, 1H), 3.73-3.75 (m,4H), 3.59-3.62 (m, 2H), 3.52-3.54 (m, 4H), 2.99-3.04 (m, 2H), 2.02- 2.03(m, 2H), 1.70-1.73 (m, 2H); LCMS (electrospray) m/z 554 (M + H)⁺. 194

Yellow solid; mp = 278.0° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 9.97 (s, 1H),8.10 (s, 1H), 7.50-7.52 (m, 2H), 6.90- 6.91 (m, 2H), 3.73-3.74 (m, 4H),3.49-3.61 (m, 6H), 2.58-2.66 (m, 2H), 1.67-1.70 (m, 2H), 1.48-1.50 (m,1H), 1.17-1.19 (m, 2H), 0.94 (d, J = 6.4 Hz, 3H); LCMS (electrospray)m/z 443 (M + H)⁺. 195

White solid; mp = 256.0° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 10.23 (s, 1H),8.14 (s, 1H),8.05 (d, J = 1.6 Hz, 1H), 7.57-7.63 (m, 2H), 7.29-7.33 (m,2H), 6.96-6.98 (m, 2H), 4.02-4.05 (m, 2H), 3.87 (d, J = 6.4 Hz, 2H),3.19- 3.27 (m, 2H), 2.60 (s, 3H), 2.09-2.10 (m, 1H), 1.88-1.91 (m, 2H),1.38-1.42 (m, 2H); LCMS (electrospray) m/z 539 (M + H)⁺. 196

Yellow solid; mp = 239.0° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 10.29 (s,1H), 8.15 (s, 1H), 8.12 (d, J = 2.0 Hz, 1H), 7.70-7.62 (m, 2H),4.04-3.96 (m, 2H), 3.84 (s, 2H), 3.620 3.56 (m, 4H), 3.28-3.22 (m, 2H),3.06 (s, 3H), 3.02- 2.94 (m, 1H), 2.82 (s, 3H), 2.56-2.50 (m, 4H),1.81-1.74 (m, 2H), 1.67-1.56 (m, 2H); LCMS (electrospray) m/z 555 (M +H)⁺. 197

White solid; mp = 259° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.25 (s, 1H),8.15 (s, 1H), 8.06 (d, J = 2.0 Hz, 1H), 8.58- 7.64 (m, 2H), 7.30-7.34(m, 2H), 7.07-7.12 (m, 2H), 3.97-4.03 (m, 2H0, 3.21-3.28 (m, 4H),3.11-3.15 (m, 2H), 3.06 (s 3H), 2.95-3.01 (m, 1H), 2.82 (s, 3H), 1.75-1.79 (m, 2H), 1.56-1.66 (m, 2H); LCMS (electrospray) m/z 577 (M + H)⁺.198

Yellow solid; mp = 269.0° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 12.66 (s,1H), 8.18 (s, 1H), 7.39 (d, J = 8.4 Hz, 2H), 6.60 (d, J = 8.4 Hz, 2H),6.32 (s, 1H), 5.36 (s, 2H), 4.02- 4.05 (m, 2H), 2.97-3.15 (m, 3H), 3.06(s, 3H), 2.82 (s, 3H), 1.77-1.80 (m, 2H), 1.59-1.66 (m, 2H); LCMS(electrospray) m/z 497 (M + H)⁺. 199

Pale yellow solid; mp = 249.9° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 10.14(brs, 1H), 8.14 (s, 1H), 7.65 (d, J = 8.4 Hz, 2H), 7.27 (d, J = 8.4 Hz,2H), 7.19 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 8.8 Hz, 2H), 3.71-3.74 (m,4H), 3.51-3.53 (m, 4H), 3.46 (s, 2H), 3.35-3.37 (m, 4H), 3.10-3.11 (m,4H); LCMS (electrospray) m/z 554, 556 (M + H)⁺ (Cl⁻ isotope pattern).200

Pale yellow solid; mp = 254.6° C.; ¹H NMR (400 MHz, DMSO- d₆) δ 10.15(brs, 1H), 8.16 (s, 1H), 7.65 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.4 Hz,2H), 7.27-7.28 (m, 4H), 3.73-3.75 (m, 4H), 3.52-3.54 (m, 4H), 3.46 (s,2H), 3.35-3.38 (m, 1H), 2.90- 2.92 (m, 2H), 1.99-2.07 (m, 2), 1.63-1.71(m, 4H); LCMS (electrospray) m/z 553, 555 (M + H)⁺ (Cl⁻ isotopepattern). 201

Yellow solid; mp = 226.3° C.; ¹H NMR (400 MHz, DMS-d₆) δ 10.22 (s, 1H),8.14 (s, 1H), 8.06 (s, 1H), 7.57-7.63 (m, 2H), 4.90 (t, J = 5.2 Hz, 1H),3.64-3.70 (m, 2H), 3.57-3.63 (m, 2H), 3.17 (s, 3H), 2.60 (s, 3H); LCMS(electrospray) m/z 389 (M + H)⁺. 202

Yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.23 (s, 1H), 8.14 (s, 1H),8.06 (s, 1H), 7.58-7.64 (m, 2H), 3.72 (t, J = 5.6 Hz, 2H), 3.60 (t, J =5.2 Hz, 2H), 3.28 (s, 3H), 3.15 (s, 3H), 2.60 (s, 3H); LCMS(electrospray) m/z 403 (M + H)⁺. 203

Ivory solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.19 9s, 1H), 8.16 (s, 1H),7.74 (s, 4H), 7.71 (d, J = 2.0 Hz, 1H), 6.64 (d, J = 2.0 Hz, 1H),3.97-4.03 (m, 2H), 3.87 (s, 3H), 3.27-3.31 (m, 2H), 3.06 (s, 3H),2.95-3.03 (m, 1H), 2.82 (s, 3H), 1.74-1.81 (m, 2H), 1.58-1.66 (m, 2H);LCMS (electrospray) m/z 494 (M + H)⁺. 204

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.26 (s, 1H), 8.75 (d, J = 2.4Hz, 1H), 8.18 (s, 1H), 7.95 (dd, J = 8.0, 2.4 Hz, 1H), 7.82-7.85 (m, 2),7.68-7.71 (m, 2H), 7.31 (d, J = 8.0 Hz, 1H), 3.99-4.02 (m, 2H),3.25-3.36 (s, 5H), 3.06 (s, 3H), 2.96-3.06 (m, 1H), 2.82 (s, 3H),1.76-1.78 (m, 2H), 1.59- 1.66 (m, 2H); LCMS (electrospray) m/z 506 (M +H)⁺. 205

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.25 (s, 1H), 8.16 (s, 1H),8.04-8.06 (m, 3H), 7.58-7.65 (m, 4H), 4.03- 4.07 (m, 2H), 3.78-3.82 (m,2H), 3.23-3.39 (m, 1H)2.60 (s, 3H), 1.93-1.96 (m, 2H), 1.61-1.67 (m,2H); LCMS (electrospray) m/z 537, 539 (M + H)⁺ (Cl⁻ isotope pattern).206

White solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.25 (s, 1H), 8.14-8.15 (m,1H), 7.99 (s, 1H), 7.65 (dd, J = 8.8, 2.0 Hz, 1H), 7.50 (d, J = 8.4 Hz,1H), 7.36-7.42 (m, 4H), 4.51-4.54 (m, 2H), 4.06-4.13 (m, 2H), 3.07-3.17(m, 2H), 2.59 (s, 3H), 1.89-1.94 (m, 1H), 1.45-1.55 (m, 4H); LCMS(electrospray) m/z 539, 541 (M + H)⁺ (Cl⁻ isotope pattern). 207

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.24 (s, 1H), 8.14 (s,1H), 8.04 (s, 1H), 7.56-7.59 (m, 2H), 7.32 (d, J = 8.8 Hz, 2H), 7.04 (d,J = 8.8 Hz, 2H), 4.67-4.69 (m, 1H), 3.79- 3.82 (m, 2H), 3.50-3.55 (m,2H), 2.58 (s, 3H), 2.03-2.04 (m, 2H), 1.73-1.75 (m, 2H); LCMS(electrospray) m/z 524 (M + H)⁺. 208

Yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.42 (s, 1H), 9.08 (s, 1H),8.72-8.74 (m, 1H), 8.24 (s, 1H), 7.86-7.95 (m, 4H), 3.99-4.02 (m, 2H),3.25-3.34 (m, 2H), 3.06 9s, 3H), 2.99-3.02 (m, 1H), 2.82 (s, 3H), 2.73(s, 3H), 1.76-1.79 (m, 2H), 1.59-1.62 (m, 2H); LCMS (electrospray) m/z506 (M + H)⁺. 209

Brown solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.33 (s, 1H), 9.10 (s, 1H),8.37 (d, J = 8.4 Hz, 1H), 8.22 (s, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.92(d, J = 8.8 Hz, 2H), 7.85 (d, J = 8.8 Hz, 2H), 3.98-4.03 (m, 2H),3.26-311 (m, 2H), 3.06 (s, 3H), 2.96- 3.01 (m, 1H), 2.82 (s, 3H),1.76-1.82 (m, 2H), 1.58-1.67 (m, 2H); LCMS (electrospray) m/z 559 (M +H)⁺. 210

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.31 (s, 1H), 8.25-8.28 (m,2H), 8.21 (s, 1H), 8.17 (s, 1H), 7.77 (d, J = 8.8 Hz, 1H), 7.69 (d, J =8.8 Hz, 1H), 7.45-7.49 (m, 2H), 3.16 (s, 6H); LCMS (electrospray) m/z439 (M + H)⁺. 211

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.16 (s, 1H), 8.16 (s,1H), 7.66 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 7.00-7.05 (m,2H), 6.92-6.95 (m, 2H), 3.73-3.76 (m, 4H), 3.61 (s, 2H), 3.54-3.57 (m,4H), 3.48-3.51 (m, 4H), 3.05-3.09 (m, 4H); LCMS (electrospray) m/z 538(M + H)⁺. 212

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.23 (s, 1H), 8.13 (s,1H), 8.04 (s, 1H), 7.78-7.79 (m, m1H), 7.56-7.61 (m, 2H), 3.96-3.99 (m,2H), 3.14-3.22 (m, 2H), 3.58 (s, 3H), 3.56 (s, 3H), 1.92-1.95 (m, 1H),1.77-1.81 (m, 2H), 1.57- 1.66 (m, m2H); LCMS (electrospray) m/z 455 (M +H)⁺. 213

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.21 (s, 1H), 8.47 (s,1H), 8.15 (s, 1H), 8.00 (d, J = 8.8 Hz, 1H), 7.80 (d, J = 8.4 Hz, 2H),7.64 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 8.8 Hz, 1H), 3.98-4.01 (m, 2H),3.88 (s, 3H), 3.23-3.27 (m, 2H), 3.05 (s, m3H), 2.95-3.00 (m, 1H), 2.81(s, 3H), 1.74-1.77 (m, 2H), 1.58-1.61 (m, 2H); LCMS (electrospray) m/z521 (M + H)⁺. 214

Yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.33 (s, 1H), 8.20-8.22 (m,3H), 8.17 (s, 1), 7.78 (d, J = 8.4 Hz, 1H), 7.69- 7.72 (m, 3H),4.02-4.04 (m, 2H), 3.19-3.22 (m, 2H), 3.06 (s, 3H), 2.99-3.01 (m, 1H),2.82 (s, 3H), 1.75-1.78 (m, 2H), 1.63-1.66 (m, 2H); LCMS (electrospray)m/z 566, 568 (M + H)⁺ (Cl⁻ isotope pattern). 215

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.23 (s, 1H), 8.15 (s,1H), 8.05 (s, 1H), 7.60-7.61 (m, 2H), 3.60-3.64 (m, 3H), 3.52-3.54 (m,2H), 3.07 (s, 3H), 2.85 (s, 3H), 2.60 (s, 3H), 2.28-2.32 (m, 1H),2.09-2.13 (m, 1H); LCMS (electrospray) m/z 566 (M + H)⁺. 216

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.28 (s, 1H), 8.54-8.56(m, 1H), 8.28-8.29 (m, 1H), 8.17 (s, 1H), 7.85 (d, J = 8.8 Hz, 2H), 7.73(d, J = 8.8 Hz, 2H), 7.25-7.28 (m, 1H), 3.99-4.02 (m, 2H), 3.22-3.25 (m,2H), 3.07 (s, 3H), 2.99-3.02 (m, 1H), 2.82 (s, 3H), 1.76-1.79 (m, 2H),1.59- 1.65 (m, 2H); LCMS (electrospray) m/z 510 (M + H)⁺. 217

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.26 (s, 1H), 8.46-8.47(m, 1H), 8.18 (s, 1H), 8.04 (d, J = 8.4 Hz, 2H), 7.81-7.84 (m, 3H),7.66-7.68 (m, 1), 3.99-4.02 (m, 2H), 3.24-3.26 (m, 2H), 3.06 (s, 3H),2.94-3.01 (m, 1H), 2.82 (s, 3H), 2.32 (s, 3H), 1.75-1.79 (m, 2H),1.57-1.66 (m, 2H); LCMS (electrospray) m/z 506 (M + H)⁺. 218

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.30 (s, 1H), 8.47 (s, 1H),8.20 (s, 1H), 8.04 (d, J = 8.4 Hz, 2H), 7.81-7.84 (m, 3H), 7.66-7.68 (m,1H), 3.73-3.76 (m, 4H), 3.53-3.56 (m, 4H), 2.32 (s, 3H); LCMS(electrospray) m/z 437 (M + H)⁺. 219

Ivory solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.26 (s, 1H), 8.14 (s, 1H),8.08 (s, 1H), 7.57-7.64 (m, 2H), 7.40-7.46 (m, 2H), 7.14-7.22 (m, 2H),4.33 (s, 2H), 3.97-4.02 (m, 2H), 3.25-3.31 (m, 2H), 3.06 (s, 3H),2.95-3.01 (m, 1H), 2.82 (s, 3H), 1.74-1.79 (m, 2H), 1.55-1.66 (m, 2H);LCMS (electrospray) m/z 563 (M + H)⁺. 220

Ivory solid; ¹H NMR (400 MHz, DMSO-d₆) δ 9.98 (s, 1H), 8.10 (s, 1H),7.l54 (d, J = 8.8 Hz, 2H), 7.08-7.13 (m, 2H), 6.99- 7.02 (m, 2H), 6.96(d, J = 8.8 Hz, 2H), 4.47-4.51 (m, 1H), 3.73-3.76 (m, 4H), 3.59-3.61 (m,1H), 3.45-3.50 (m, 4H), 3.45-3.49 (m, 1H), 2.97-3.09 (m, 2H), 2.00-2.06(m, 2H), 1.66-1.75 (m, 2H); LCMS (electrospray) m/z 539 (M + H)⁺. 221

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.18 (s, 1H), 8.34-8.36 (m,1H), 8.04-8.06 (m, 2H), 7.57-7.62 (m, 2H), 3.61-3.65 (m, 1H), 2.59 (s,3H), 1.95-1.97 (m, 2H), 1.69- 1.74 (m, 2H), 1.55-1.61 (m, 1H), 1.17-1.38(m, 4H); LCMS (electrospray) m/z 413 (M + H)⁺. 222

Yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.28 (s, 1H), 10.24 (s, 1H),8.16 (s, 1H), 8.05 (s, 1H), 8.03 (d, J = 2.0 Hz, 1H), 7.58-7.61 (m, 3H),7.45-7.48 (m, 1H), 3.70-3.82 (m, 3H), 3.51-3.64 (m, 2H), 2.60 (s, 3H),2.59 (s, 3H), 2.38- 2.44 (m, 1H), 2.26-2.33 (m, 1H); LCMS (electrospray)m/z 559 (M + H)⁺. 223

Yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.24 (s, 1H), 9.15 (s, 1H),8.05 (s, 1H), 7.60-7.64 (m, 2H), 3.59-3.72 (m, 3H), 3.48-3.58 (m, 2H),3.70 (s, 3H), 2.86 (s, 3H), 2.60 (s, 3H), 2.24-2.34 (m, 1H), 2.07-2.16(m, 1H); LCMS (electrospray) m/z 456 (M + H)⁺. 224

Ivory solid; ¹H NMR (400 MHz, CDCl₃) δ 7.86 (d, J = 2.0 Hz, 1H), 7.66(s, 1H), 7.63 (s, 1H), 7.54 (dd, J = 8.4, 2.0 Hz, 1H), 7.43 (d, J = 8.4Hz, 1H), 6.09 (brs, 1H), 3.70-3.75 (m, 4H), 3.44-3.49 (m, 2H), 2.64-2.69(m, 2H), 2.63 (s, 3H), 2.48- 2.53 (m, 4H); LCMS (electrospray) m/z 444(M + H)⁺. 225

White solid; ¹H NMR (400 MHz, CDCl₃) δ 7.87 (d, J = 2.0 Hz, 1H), 7.65(s, 1H), 7.60 (s, 1H), 7.55 (dd, J = 8.8, 2.0 Hz, 1H), 7.44 (d, J = 8.8Hz, 1H), 3.66-3.71 (m, 6H), 3.19 (s, 3H), 2.63- 2.66 (m, 2H), 2.64 (s,3H), 2.52-2.54 (m, 4H); LCMS (electrospray) m/z 458 (M + H)⁺. 226

Yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.00 (s, 1H), 8.10 (s, 1H),8.03 (d, J = 9.2 Hz, 2H), 7.62 (d, J = 9.2 Hz, 2H), 7.53 (d, J = 8.8 Hz,2H), 6.95 (d, J = 8.8 Hz, 2H), 3.72-3.74 (m, 4H), 3.68-3.69 (m, 2H),3.50-3.53 (m, 4)HH), 2.80-2.87 (m, 3H), 1.94-1.97 (m, 2H), 1.66-1.70 (m,2H); LCMS (electrospray) m/z 567, 569 (M + H)⁺ (Cl⁻ isotope pattern).227

Pale yellow solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.51 (s, 1H), 8.15 (s,1H), 7.98 (s, 1H), 7.64-7.66 (m, 1H), 7.48 (d, J = 8.8 Hz, 1H), 4.03(brs, 1H), 3.77-3.80 (m, 3H), 3.61-3.64 (m, 2H), 2.58 (s, 3H), 1.86-1.94(m, 4H), 1.64-1.73 (m, 3H), 1.38-1.48 (m, 2H), 1.24-1.29 (m, 1H); LCMS(electrospray) m/z 457 (M + H)⁺. 228

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.23 (s, 1H), 8.15 (s,1H), 7.92 (m, 1H), 7.78 (d, J = 8.4 Hz, 2H), 7.69 (d, J = 8.4 Hz, 2H),3.97-4.01 (m, 2H), 3.80 (s, 3H), 3.23- 3.26 (m, 2H), 3.05 (s, 3H),2.94-3.00 (m, 1H), 2.80 (s, 3H), 1.74-1.77 (m, 2H), 1.55-1.65 (m, 2H);LCMS (electrospray) m/z 512 (M + H)⁺. 229

Yellow solid; ¹H NMR (400 MHz, acetone-d₆) δ 8.15 (brs, 1H), 7.83 (s,1H), 7.62 (d, J = 1.2 Hz, 1H), 7.48 (d, J = 8.0 Hz, 1H), 7.36 (dd, J =8.0, 1.2 Hz, 1H), 4.65 (d, J = 6.0 Hz, 2H), 3.77- 3.80 (m, 4H),3.54-3.56 (m, 4H), 2.57 (s, 3H); LCMS (electrospray) m/z 415 (M + H)⁺.230

Pale yellow solid; ¹H NMR (400 MHz, acetone-d₆) δ 8.48 (s, 1H), 8.06 (d,J = 2.0 Hz, 1H), 7.57-7.59 (m, 1H), 7.44 (d, J = 8.8 Hz, 1H),l 6.84-6.85(m, 2H), 3.78-3.;81 (m, 4H), 3.56- 3.58 (m, 4H), 2.57 (s, 3H); LCMS(electrospray) m/z 416 (M + H)⁺. 231

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.45 (s, 1H), 8.94 (d, J = 2.0Hz, 1H), 8.21 (dd, J = 8.4, 2.0 Hz, 1H), 8.18 (s, 1H), 8.09-8.13 (m,2H), 7.95 (d, J = 8.4 Hz, 1H), 7.28-7.32 (m, 2H), 3.98-4.02 (m, 2H),3.25-3.37 (m, 2H), 3.06 (s, 3H), 2.94-3.02 (m, 1H), 2.82 (s, 3H),1.75-1.79 (m, 2H), 1.59- 1.65 (m, 2H); LCMS (electrospray) m/z 510 (M +H)⁺. 232

Pale yellow solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.49 (s, 1H), 8.15 (s,1H), 7.98 (s, 1H), 7.65 (d, J = 8.8 Hz, 1H), 7.50 (d, J = 8.8 Hz, 1H),4.18-4.25 (m, 1H), 4.04-4.07 (m, 1H), 3.79- 3.84 (m, 2H), 3.59-3.62 (m,2H), 2.59 (s, 3H), 1.34 (d, J = 6.8 Hz, 6H); LCMS (electrospray) m/z 416(M + H)⁺. 233

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.23 (s, 1H), 8.13 (s, 1H),8.03 (s, 1H), 7.56-7.61 (m, 2H), 6.90-6.92 (m, 1H), 3.89-3.93 (m, 2H),3.55 (m, 1H), 3.22-3.29 (m, 2H), 2.58 (s, 3H), 1.82-1.85 (m, 2H),1.43-1.45 (m, 2H), 1.38 (s, 9H); LCMS (electrospray) m/z 513 (M + H)⁺.234

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.20 (s, 1H), 8.11 (s,1H), 8.03 (s, 1H), 7.55-7.61 (m, 2H), 3.86-3.90 (m, 2H), 3.18-3.24 (m,2H), 2.81-2.84 (m, 1H), 2.58 (s, 3H), 1.77-1.80 (m, 2H), 1.68 (s, 2H),1.25-1.33 (m, 2H); LCMS (electrospray) m/z 413 (M + H)⁺. 235

Pale pink solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.20 (s, 1H), 98.13 (s,1H), 7.69-7.73 (m, 2H), 7.33-7.35 (m, 2H), 7.16- 7.20 (m, 2H), 7.04-7.06(m, 2H), 4.69-4.70 (m, 1H), 3.80- 3.83 (m, 2H), 3.54-3.56 (m, 2H),1.99-2.05 (m, 2H), 1.74- 1.77 (m, 2H); LCMS (electrospray) m/z 487 (M +H)⁺. 236

Ivory solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.23 (s, 1H), 8.13 (s, 1H),8.05 (s, 1H), 7.57-7.63 (m, 2H), 7.33 (d, J = 8.0 Hz, 2H), 7.21 (d, J =8.4 Hz, 2H), 3.95-4.02 (m, 2H), 3.09- 3.17 (m, 2H), 2.59 (s, 3H), 2.55(d, J = 7.2 Hz, 2H), 1.80-1.85 (m, 1H), 1.66-1.69 (m, 2H), 1.23-1.32 (m,2H); LCMS (electrospray) m/z 523 (M + H)⁺. 237

Ivory solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.27 (s, 1H), 8.16 (s, 1H),8.05 (s, 1H), 7.28-7.62 (m, 2H), 3.55-3.60 (m, 4H), 3.24-3.29 (m, 4H),2.78 (s, 6H), 2.60 (s, 3H); LCMS (electrospray) m/z 470 (M + H)⁺. 238

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.23 (s, 1H), 8.14 (s, 1H),8.06 (s, 1H), 7.60-7.61 (m, 2H), 4.58-4.61 (m, 1H), 3.59-3.60 (m, 2H),3.46-3.50 (m, 2H), 3.13 (s, 3H), 2.60 (s, 3H), 1.78-1.81 (m, 2H); LCMS(electrospray) m/z 403 (M + H)⁺. 239

Pale yellow solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.51 (s, 1H), 8.13 (s,1H), 7.95-7.96 (m, 1H), 7.78 (brs, 1H), 7.63- 7.65 (m, 1H), 7.47-7.51(m, 1H), 7.36-7.37 (m, 2H), 6.89- 6.92 (m, 2H), 4.60 (s, 2H), 3.78 (s,3H), 2.58 (s, 3H); LCMS (electrospray) m/z 451 (M + H)⁺. 240

Beige solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.52 (s, 1H), 8.75 (d, J =1.6 Hz, 1H), 8.01 (s, 1H), 7.90-7.92 (m, 3H), 7.65- 7.67 (m, 2H), 7.30(d, J = 8.0 Hz, 1H), 3.20 (s, 6H), 2.52 (s, 3H); LCMS (electrospray) m/z395 (M + H)⁺. 241

Pale yellow solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.47 (s, 1H),8.08-8.10 (m, 2H), 7.98 (s, 1H), 7.77-7.80 (m, 2H), 7.58-7.60 (m, 2H),7.08-7.13 (m, 2), 4.14-4.18 (m, 2H), 3.82-3.88 (m, 1H), 3.40-3.48 (m,2H), 3.09-3.11 (m, 2H), 1.81-1.89 (m, 2H); LCMS (electrospray) m/z 500,502 (M + H)⁺ (Cl⁻ isotope pattern). 242

White solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.52 (s, 1H), 8.15 (s, 1H),7.99 (s, 1H), 7.64-7.66 (m, 1H), 7.49-7.51 (m, 1H), 4.17-4.23 (m, 1H),3.63-3.65 (m, 4H), 3.34 (s, 3H), 2.59 (s, 3H), 1.33 (d, J = 6.8 Hz, 6H);LCMS (electrospray) m/z 430 (M + H)⁺. 243

Pale beige solid; ¹H NMR (400 MHz, DMSO-d₆) δ 12.48 (s, 1H), 10.40 (s,1H), 8.26 (s, 1H), 8.06 (s, 1H), 7.59-7.64 (m, 2H), 2.59 (s, 3H),2.44-2.48 (m, 2H), 1.59-1.68 (m, 2H), 0.89-0.93 (m, 3H); LCMS(electrospray) m/z 400 (M + H)⁺. 244

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.28 (s, 1H), 8.16 (s,1H), 8.05 (s, 1H), 7.58-7.63 (m, 2H), 4.31-4.35 (m, 2H), 4.19-4.23 (m,2H), 3.97-4.02 (m, 1H), 2.89 (s, 3H), 2.86 (s, 3H), 2.60 (s, 3H); LCMS(electrospray) m/z 442 (M + H)⁺. 245

Pale yellow solid; ¹H NMR (400 MHz, CDCl₃ + MeOD-d₄) δ 7.68 (s, 1H),7.48-7.51 (m, 2H), 7.12 (d, J = 8.8 Hz, 2H), 6.91- 6.95 (m, 2H), 6.71(d, J = 8.8 Hz, 2H), 4.01-4.05 (m, 2H), 3.73 (d, J = 6.0 Hz, 2H),3.07-3.13 (m, 2H), 1.88-2.03 (m, 3H), 1.37-1.48 (m, 2H); LCMS(electrospray) m/z 502 (M + H)⁺. 246

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.93 (s, 1H), 8.69 (s,1H), 8.39 (s, 1H), 8.21 (d, J = 8.4 Hz, 1H), 8.13 (d, J = 8.4 Hz, 1H),7.78-7.81 (m, 2H), 7.31-7.35 (m, 2H), 3.99- 4.03 (m, 2H), 3.07 (s, 3H),2.99-3.01 (m, 1H), 2.82 (s, 3H), 1.94-1.97 (m, 2H), 1.76-1.79 (m, 2H),1.60-1.63 (m, 2H); LCMS (electrospray) m/z 510 (M + H)⁺. 247

Pale ivory solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.45 (s, 1H), 7.95 (s,1H), 7.76-7.80 (m, 2H), 7.35-7.41 (m, 4H), 7.08- 7.12 (m, 2H), 4.52-4.53(m, 2H), 4.07-4.09 (m, 2H), 3.;09- 3.13 (m, 3H), 1.90-2.05 (m, 2H),1.47-1.51 (m, 2H); LCMS (electrospray) m/z 502, 504 (M + H)⁺ (Cl⁻isotope pattern). 248

Yellow solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.54 (s, 1H), 8.15 (s, 1H),7.99 (s, 1H), 7.654 (d, J = 8.8 Hz, 1H), 7.50 (d, J = 8.8 Hz, 1H), 7.33(d, J = 7.6 Hz, 2H), 6.92 (d, J =7.6 Hz, 2H), 4.84 (s, 2H), 4.10 (s,1H), 3.83-3.86 (m, 2H), 3.79 (s, 3H), 3.67-3.69 (m, 2H), 2.59 (s, 3H);LCMS (electrospray) m/z 495 (M + H)⁺. 249

Brown solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.30 (s, 1H), 8.24-8.28 (m,2H), 8.21 (d, J = 2.0 Hz, 1H), 8.16 (s, 1H), 7.76 (d, J = 8.8 Hz, 1H),7.69 (dd, J = 8.8, 2.0 Hz, 1H), 7.43-7.50 (m, 2H), 4.87-4.91 (m, 1H),3.65-3.69 (m, 2H), 3.57-3.62 (m, 2H), 3.17 (s, 3H); LCMS (electrospray)m/z 468(M + H)⁺. 250

Green solid; ¹H NMR (400 MHz, DMSO-d₆) δ 9.30 (s, 1H), 8.07 (s, 1H),7.54 (d, J = 9.2 Hz, 2H), 7.08-7.13 (m, 2H), 6.99- 7.02 (m, 2H), 6.96(d, J = 9.2 Hz, 2H), 4.87-4.90 (m, 1H), 4.47-4.51 (m, 1H), 3.64-3.66 (m,2H), 3.56-3.59 (m, 2H), 3.44-3.49 (m, 2H), 3.16 (s, 3H), 2.97-3.03 (m,2H), 2.00- 2.06 (m, 2H), 1.48-1.57 (m, 2H); LCMS (electrospray) m/z 526(M + H)⁺. 251

Ivory solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.23 (s, 1H), 8.13 (s, 1H),8.08 (s, 1H), 7.60-7.64 (m, 2H), 7.41-7.43 (m, 2H), 7.15-7.22 (m, 2H),4.87-4.91 (m, 1H), 4.33 (s, 2H), 3.63-3.67 (m, 2H), 3.57-3.61 (m, 2H),3.17 (s, 3H); LCMS (electrospray) m/z 482 (M + H)⁺. 252

Ivory solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.22 (s, 1H), 8.14 (s, 1H),8.06 (d, J = 2.0 Hz, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.59 (dd, J = 8.4,2.0 Hz, 1H), 7.30-7.35 (m, 2H), 7.07-7.12 (m, 2H), 4.87-4.91 (m, 1H),3.64-3.69 (m, 2H), 3.57-3.61 (m, 2H), 3.22-3.26 (m, 2H), 3.17 (s, 3H),3.10-3.15 (m, 2H); LCMS (electrospray) m/z 496 (M + H)⁺. 253

Pale yellow solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.51 (s, 1H), 8.15 (s,1H), 7.99 (s, 1H), 7.64-7.66 (m, 1H), 7.48-7.51 (m, 1H), 3.68-3.71 (m,2H), 3.21 (s, 3H), 2.60 (s, 3H), 2.58- 2.84 (m, 2H), 2.25 (s, 6H); LCMS(electrospray) m/z 415 (M + H)⁺. 254

Pale yellow solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.48 (s, 1H),8.13-8.14 (m, 1H), 7.97 (s, 1H), 7.63-7.66 (m, 1H), 7.48-7.51 (m, 1H),3.63-3.67 (m, 2H), 3.42-3.45 (m, 2H), 3.29 (s, 3H), 3.18 (s, 3H), 2.58(s, 3H), 1.94-1.97 (m, 2H); LCMS (electrospray) m/z 417 (M + H)⁺. 255

Pale yellow solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.31 (s, 1H),8.16-8.17 (m, 1H), 7.64-7.67 (m, 2H), 7.46-7.49 (m, 1H), 4.61 (t, J =8.0 Hz, 2H), 3.74 (t, J = 8.0 Hz, 2H), 3.47- 3.52 (m, 1H), 3.03 (s, 3H),2.57 (s, 3H), 1.19 (d, J = 6.8 Hz, 6H); LCMS (electrospray) m/z 431 (M +H)⁺. 256

Pale yellow solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.51 (s, 1H),8.14-8.15 (m, 1H), 8.00 (s, 1H), 7.64-7.66 (m, 1H), 7.48 (d, J = 8.8 Hz,1H), 7.26-7.30 (m, 2H), 6.92-6.98 (m, 3H), 4.33(t, J = 5.6 Hz, 2H), 4.02(t, J = 5.6 Hz, 2H), 3.13 (s, 3H), 2.59 (s, 3H); LCMS (electrospray) m/z465 (M + H)⁺. 257

Pale yellow solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.49 (s, 1H), 8.14 (s,1H), 7.98 (s, 1H), 7.63 (d, J = 8.8 Hz, 1H), 7.48 (d, J = 8.8 Hz, 1H),3.50 (t, J = 6.4 Hz, 2H), 3.17 (s, 3H), 2.77- 2.81 (m, 2H), 2.66 (t, J =6.4 Hz, 2H), 2.58 (s, 3H), 1.95-1.99 (m, 2H), 1.29 1.32 (m, 2H); LCMS(electrospray) m/z 428 (M + H)⁺. 258

Orange solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.42 (s, 1H), 8.59 (s, 1H),8.23 (s, 1H), 8.04-8.06 (m, 4H), 7.90-7.93 (m, 2H), 3.99-4.02 (m, 2H),3.25-3.31 (m, 2H), 3.06 (s, 3H), 2.97-3.00 (m, 1H), 2.82 (s, 3H), 2.41(s, 3H), 1.75-1.79 (m, 2H), 1.60-1.62 (m, 2H). 259

Bright yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.59 (s, 1H), 9.00 (d,J = 2.0 Hz, 1H), 8.59 (dd, J = 8.8, 2.0 Hz, 1H), 8.24 (s, 1H), 8.09-8.12(m, 2H), 8.01 (d, J = 8.8 Hz, 1H), 7.30- 7.35 (m, 2H), 3.99-4.02 (m,2H), 3.25-3.31 (m, 2H), 3.06 (s, 3H), 2.99-3.06 (m, 1H), 2.82 (s, 3H),1.76-1.79 (m, 2H), 1.59-1.63 (m, 2H). 260

Yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.21 (s, 1H), 8.47 (d, J =2.0 Hz, 1H), 8.37 (s, 1H), 8.10 (s, 1H), 8.06 (d, J = 8.4 Hz, 2H), 7.84(d, J = 8.4 Hz, 1H), 7.80 (d, J = 8.4 Hz, 2H), 7.67 (dd, J = 8.4, 2.0Hz, 1H), 3.56-3.58 (m, 4H), 3.46-3.50 (m, 2H), 2.50-2.55 (m, 2H),2.40-2.44 (m, 4H), 2.32 (s, 3H); LCMS (electrospray) 479 m/z (M + H)⁺.261

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.27 (s, 1H), 8.16 (s, 1H),8.05 (s, 1H),l 7.61-7.63 (m, 2H), 6.67 (s, 1H), 4.42-4.48 (m, 1H),3.89-3.93 (m, 1H), 3.61-3.67 (m, 1H), 3.19 (s, 3H), 2.60 (s, 3H); LCMS(electrospray) m/z 456 (M + H)⁺. 262

Ivory solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.25 (s, 1H), 8.47 (d, J = 2.0Hz, 1H), 8.17 (s, 1H), 8.06 (d, J = 8.4 Hz, 2H), 7.84 (d, J = 8.4 Hz,1H), 7.81 (d, J = 8.4 Hz, 2H), 7.68 (dd, J = 8.4, 2.0 Hz, 1H), 3.70-3.74(m, 2H), 3.58-3.62 (m, 2H), 3.28 (s, 3H), 3.15 (s, 3H), 2.32 (s, 3H);LCMS (electrospray) m/z 438 (M + H)⁺. 263

Ivory solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.05 (s, 1H), 8.03 (s, 1H),7.83 (s, 1H), 7.56-7.62 (m, 2H), 5.63-5.68 (m, 1H), 3.97-4.02 (m, 1H),3.80-3.84 (m, 1H), 2.97 (s, 3H), 2.59 (s, 3H), 2.43 (s, 3H); LCMS(electrospray) m/z 470 (M + H)⁺. 264

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.21 (s, 1H), 8.13 (s,1H), 8.04 (s, 1H), 7.56-7.61 (m, 2H), 3.71-3.75 (m, 2H), 3.12 (s, 3H),2.95 (s, 3H), 2.80 (s, 3H), 2.69-2.72 (m, 2H), 2.58 (s, 3H); LCMS(electrospray) m/z 443 (M + H)⁺. 265

Yellow solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.48 (s, 1H), 8.44 (s, 1H),7.99 (s, 1H), 7.96 (d, J = 8.8 Hz, 1H), 7.88 (d, J = 8.8 Hz, 2H), 7.62(d, J = 8.8 Hz, 2H), 6.84 (d, J = 8.8 Hz, 1H), 3.93 (s, 3H), 3.78 (t, J= 5.2 Hz, 2H), 3.67 (t, J = 5.2 Hz, 2H), 3.33 (s, 3H), 3.22 (s, 3H);LCMS (electrospray) m/z 454 (M + H)⁺. 266

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.20 (brs, 1H), 8.50(brs, 1H), 8.04-8.07 (m, 2H), 7.59-7.62 (m, 2H), 3.51-3.54 (m, 5H),3.29-3.31 (m, 2H), 2.60 (s, 3H); LCMS (electrospray) m/z 388 (M + H)⁺.267

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.19 (s, 1H), 8.46 (brt,J = 5.2 Hz, 1H), 8.05-8.07 (m, 2H), 7.59-7.60 (m, 2), 4.83 (t, J = 5.2Hz, 1H), 3.57-3.61 (m, 2H), 3.40- 3.44 (m, 2H), 2.59 (s, 3H); LCMS(electrospray) m/z 374 (M + H)⁺. 268

solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.30 (s, 1H), 8.62 (d, J = 2.4 Hz,1H), 8.18 (s, 1H), 8.00-8.06 (m, 3H), 7.77-7.85 (m, 3H), 3.99-4.02 (m,2H), 3.25-3.32 (m, 2H), 3.06 (s, 3H), 2.96-3.06 (m, 1H), 2.82 (s, 3H),l1.76-1.79 (m, 2H), 1.56- 1.66 (m, 2H); LCMS (electrospray) m/z 510 (M +H)⁺. 269

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 9.95 (s, 1H), 8.01 (s, 1H),7.78 (s, 1H), 7.56-7.57 (m, 2H), 4.54 (t, J = 8.0 Hz, 2H), 3.63 (t, J =8.0 Hz, 2H), 3.36 (q, J = 6.8 Hz, 2H), 2.57 (s, 3H), 2.39 (s, 3H), 1.13(t, J = 6.8 Hz, 3H); LCMS (electrospray) m/z 417 (M + H)⁺. 270

Pale yellow solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.98 (s, 1H), 8.03 (s,1H), 7.80 (s, 1H), 7.57-7.59 (s, 2H), 4.50 (t, J = 7.6 Hz, 2H), 3.61 (t,J = 7.6 Hz, 2H), 2.68-2.72 (m, 1H), 2.59 (s, 3H), 2.45 (s, 3H),0.74-0.79 (m, 4H). 271

Pale yellow solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.53 (s, 1H),8.49-8.50 (m, 1H), 8.20-8.25 (m, 1H), 8.00 (s, 1H), 7.92 (d, J = 9.2 Hz,2H), 7.68 (d, J = 9.2 Hz, 2H), 7.14-7.17 (m, 1H), 3.77-3.79 (m, 2H),3.66-3.68 (m, 2H), 3.33 (s, 3H), 2.22 (s, 3H); LCMS (electrospray)m/z443 (M + H)⁺. 272

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.26 (s, 1H), 8.54-8.55(m, 1H), 8.28-8.29 (m, 1H), 8.17 (s, 1H), 7.85 (d, J = 8.8 Hz, 2H), 7.72(d, J = 8.8 Hz, 2H), 7.25-7.28 (m, 1H), 4.90 (s, 1H), 3.65-3.67 (m, 2H),3.60-3.61 (m, 2H), 3.18 (s, 3H); LCMS (electrospray) m/z 429 (M + H)⁺.273

Pale yellow solid; ¹H NMR (400 MHz, methanol-d₆) δ 8.58- 8.59 (m, 1H),8.21-8.23 (m, 1H), 8.03-8.06 (m, 1H), 8.01 (s, 1H), 7.66-7.70 (m, 2H),7.19-7.24 (m, 2H), 3.77-3.80 (m, 2H), 3.68-3.70 (m, 2H), 3.38 (s, 3H),3.23(s, 3H); LCMS (electrospray) m/z 443 (M + H)⁺. 274

Yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 9.93 (s, 1H), 8.07 (s, 1H),8.03 (d, J = 8.8 Hz, 2H), 7.62 (d, J = 8.8 Hz, 2H), 7.53 (d, J = 9.2 Hz,2H), 6.94 (d, J = 9.2 Hz, 2H), 4.89 (s, 1H), 3.71-3.72 (m, 1H),3.64-3.68 (m, 3H), 3.59-3.60 (m, 3H), 3.16 (s, 3H), 2.81-2.84 (m, 2H),1.85-1.88 (m, 2H), 1.67- 1.69 (m, 2H); LCMS (electrospray) m/z 443, 445(M + H)⁺ (Cl⁻ isotope pattern). 275

Ivory solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.15 (s, 1H), 8.14 (s, 1H),7.70-7.73 (m, 5H), 6.63 (s, 1H), 4.87-4.91 (m, 1H), 3.87 (s, 3H),3.64-3.69 (m, 2H), 3.58-3.62 (m, 2H), 3.17 (s, 3H); LCMS (electrospray)m/z 413 (M + H)⁺. 276

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.25 (s, 1H), 8.16 (s,1H), 8.01 (s, 1H), 7.78 (s, 4H), 3.97-4.01 (m, 2H), 3.85 (s, 3H),3.23-3.27 (m, 2H), 3.10 (s, 3H), 2.98-3.05 (m, 1H), 2.81 (s, 3H),1.74-1.77 (m, 2H), 1.56-1.64 (m, 2H); LCMS (electrospray) m/z 528 (M +H)⁺. 277

Pale beige solid; ¹H NMR (400 MHz, DMSO-d₆) d 10.28 (s, 1H), 8.54-8.55(m, 1H), 8.27-8.28 (m, 1H), 8.17 (s, 1H), 7.85 (d, J = 8.8 Hz, 2H), 7.72(d, J = 8.8 Hz, 2H), 7.25-7.28 (m, 1H), 3.99-4.02 (m, 2H), 3.25-3.26 (m,2H), 3.06 (s, 3H), 2.98-2.99 (m, 1H), 2.82 (s, 3H), 2.49 (s, 3H),1.76-1.79 (m, 2H), 1.60-1.62 (m, 2H); LCMS (electrospray) m/z 510 (M +H)⁺. 278

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.23 (s, 1H), 8.49 (s,1H), 8.17 (s, 1H), 8.02 (d, J = 8.4 Hz, 1H), 7.81 (d, J = 8.4 Hz, 2H),7.66 (d, J = 8.4 Hz, 2H), 6.91 (d, J = 8.4 Hz, 1H), 3.99-4.02 (m, 2H),3.90 (s, 3H), 3.28-3.31 (m, 2H), 3.07 (s, 3H), 2.99-3.02 (m, 1H), 2.82(s, 3H), 2.32 (s, 3H), 1.76-1.79 (m, 2H), 1.57-1.67 (m, 2H); LCMS(electrospray) m/z 521 (M + H)⁺. 279

Pale yellow solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.49 (s, 1H), 7.99 (s,1H), 7.84-7.91 (m, 4H), 7.81 (s, 1H), 4.04-4.05 (m, 1H), 3.92 (s, 3H),3.84-3.87 (m, 2H), 3.69-3.74 (m, 2H), 3.25 (s, 3H); LCMS (electrospray)m/z 447 (M + H)⁺. 280

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 13.20 (s, 1H), 10.25 (s,1H), 8.14 (s, 1H), 7.78 (s, 4H), 3.96-3.99 (m, 2H), 3.21-3.24 (m, 2H),3.04 (s, 3H), 2.93-2.98 (m, 1H), 2.79 (s, 3H), 1.73-1.76 (m, 2H),1.54-1.64 (m, 2H); LCMS (electrospray) m/z 514 (M + H)⁺. 281

Pale yellow solid; ¹H NMR (400 MHz, acetone-d₆) δ 12.19 (s, 1H), 9.55(s, 1H), 8.01 (s, 1H), 7.85-7.91 (m, 4H), 7.78 (s, 1H), 4.04-4.05 (m,1H), 3.84-3.88 (m, 2H), 3.70-3.73 (m, 2H), 3.25 (s, 3H); LCMS(electrospray) m/z 433 (M + H)⁺. 282

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.42 (s, 1H), 8.65 (s,1H), 8.16-8.24 (m, 3H), 8.01 (d, J = 8.8 Hz, 2H), 7.93 (d, J = 8.8 Hz,2H), 3.98-4.01 (m, 2H), 3.27-3.30 (m, 2H), 3.05 (s, 3H), 2.95-3.01 (m,1H), 2.80 (s, 3H), 2.44 (s, 3H), 2.31 (s, 3H), 1.74-1.77 (m, 2H),1.55-1.64 (m, 2H); LCMS (electrospray) m/z 505 (M + H)⁺. 283

Yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.98 (s, 1H), 8.69 (s, 1H),8.39 (s, 1H), 8.14-8.21 (m, 2H), 7.78-7.81 (m, 2H), 7.31-7.35 (m, 2H),4.00-4.03 (m, 2H), 3.26-3.32 (m, 2H), 3.07 (s, 3H), 2.98-2.99 (m, 1H),2.82 (s, 3H), 2.32 (s, 3H), 1.76-1.79 (m, 2H), 1.60-1.62 (m, 2H); LCMS(electrospray) m/z 510 (M + H)⁺. 284

Yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.29 (s, 1H), 8.63 (s, 1H),8.18 (s, 1H), 8.04-8.06 (m, 2H), 8.01-8.03 (m, 1H), 7.84-7.86 (m, 2H),7.78-7.81 (m, 1H), 3.99-4.03 (m, 2H), 3.25-3.31 (m, 2H), 3.07 (s, 3H),2.96-3.02 (m, 1H), 2.82 (s, 3H), 2.31 (s, 3H), 1.76-1.79 (m, 2H),1.58-1.66 (m, 2H); LCMS (electrospray) m/z 509 (M + H)⁺. 285

Pale brown solid; ¹H NMR (400 MHz, DMSO-d₆) δ 9.97 (s, 1H), 8.06 (s,1H), 7.37 (s, 1H), 7.21 (d, J = 8.8 Hz, 1H), 6.90 (d, J = 8.8 Hz, 1H),3.73 (s, 3H), 3.71 (s, 3H), 3.52-3.54 (m, 4H), 1.60-1.62 (m, 6H); LCMS(electrospray) m/z 403 (M + H)⁺. 286

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 9.28 (s, 1H), 8.04 (s,1H), 7.41 (d, J = 8.8 Hz, 1H), 6.62 (s, 1H), 6.50 (d, J = 8.8 Hz, 1H),3.78 (s, 3H), 3.75 (s, 3H), 3.51-3.53 (m, 4H), 1.60-1.62 (m, 6H); LCMS(electrospray) m/z 403 (M + H)⁺. 287

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 9.99 (s, 1H), 8.08 (s, 1H),7.58-7.61 (m, 2H), 6.90-6.93 (m, 2H), 3.74 (s, 3H), 3.53 (q, J = 7.2 Hz,4H), 1.21 (t, J = 7.2 Hz, 6H); LCMS (electrospray) m/z 362 (M + H)⁺. 288

Ivory solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.24 (s, 1H), 8.55 (d, J = 2.8Hz, 1H), 8.39 (s, 1H), 8.24-8.30 (m, 1H), 8.10 (s, 1H), 7.85 (d, J = 8.4Hz, 2H), 7.73 (d, J = 8.4 Hz, 2H), 7.27 (dd, JU = 8.4, 2.8 Hz, 1H),3.56-3.60 (m, 4H), 3.46-3.49 (m, 2H), 2.50-2.55 (m, 2H), 2.39-2.46 (m,4H); LCMS (electrospray) m/z 484 (M + H)⁺. 289

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.26 (s, 1H), 8.54 (s,1H), 8.24-8.27 (m, 1H), 8.16 (s, 1H), 7.83 (d, J = 8.8 Hz, 2H), 7.71 (d,J = 8.8 Hz, 2H), 7.24-7.27 (m, 1H), 3.44- 3.47 (m, 4H), 2.78-2.81 (m,4H); LCMS (electrospray) m/z 439 (M + H)⁺. 290

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.20 (s, 1H), 8.66 (s,1H), 8.07 (s, 1H), 8.03 (s, 1H), 7.56-7.61 (m, 2H), 7.32 (d, J = 8.4 Hz,2H), 6.99 (d, J = 8.4 Hz, 2H), 4.15- 4.17 (m, 2H), 3.72-3.73 (m, 2H),2.49 (s, 3H); LCMS (electrospray) m/z 484 (M + H)⁺. 291

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.26 (s, 1H), 8.56 (s, 1H),8.28-8.29 (m, 1H), 8.17 (s, 1H), 7.85 (d, J =8.8 Hz, 2H), 7.73 (d, J =8.8 Hz, 2H), 7.26-7.29 (m, 1H), 4.60 (s, 1H), 3.57-3.60 (m, 2H),3.47-3.50 (m, 2H), 3.25 (s, 3H), 1.78-1.81 (m, 2H); LCMS (electrospray)m/z 443 (M + H)⁺. 292

Ivory solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.18 (s, 1H), 8.48 (d, J = 2.4Hz, 1H), 8.37 (brs, 1H), 8.09 (s, 1H), 8.01 (dd, J 9.2, 2.4 Hz, 1H),7.81 (d, J = 8.8 Hz, 2H), 7.66 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 9.2 Hz,1H), 3.89 (s, 3H), 3.56-3.58 (m, 4H), 3.45-3.50 (m, 2H), 2.51-2.54 (m,2H), 2.39-2.44 (m, 4H); LCMS (electrospray) m/z 496 (M + H)⁺. 293

Ivory solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.24 (s, 1H), 8.62 (d, J = 2.0Hz, 1H), 8.39 (brs, 1H), 8.10 (s, 1H), 7.99- 8.05 (m, 3H), 7.77-7.84 (m,3H), 3.56-3.60 (m, 4H), 3.43- 3.48 (m, 2H), 2.52-2.55 (m, 2H), 2.39-2.45(m, 4H); LCMS (electrospray) m/z 483 (M + H)⁺. 294

Ivory solid; ¹H NMR (400 MHz, DMSO-d₆) δ 9.87 (s, 1H), 8.31 (brs, 1H),7.99 (s, 1H), 7.49 (d, J = 8.8 Hz, 2H), 7.16-7.29 (m, 5H), 6.90 (d, J =8.8 Hz, 2H), 4.31 (s, 1H), 3.55-3.59 (m, 4H), 3.43-3.48 (m, 2H),3.29-3.36 (m, 2H), 2.93-3.01 (m, 2H), 2.70 (s, 2H), 2.50-2.59 (m, 2H),2.37-2.43 (m, 4H), 1.55- 1.64 (m, 2H), 1.42-1.49 (m, 2H); LCMS(electrospray) m/z 578 (M + H)⁺. 295

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 9.91 (s, 1H), 8.32 (brs,1H), 8.00 (s, 1H), 7.53 (d, J = 8.8 Hz, 2H), 7.07- 7.14 (m, 2H),6.97-7.03 (m, 2H), 6.95 (d, J = 8.8 Hz, 2H), 4.45-4.50 (m, 1H),3.55-3.60 (m, 4H), 3.43-3.50 (m, 4H), 2.95-3.03 (m, 2H), 2.50-2.55 (m,2H), 2.39-2.43 (m, 4H), 1.96-2.06 (m, 2H), 1.68-1.75 (m, 2H); LCMS(electrospray) 582 m/z (M + H)⁺. 296

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.20 (s, 1H), 8.42 (brs, 1H),8.07 (s, 1H), 8.05 (s, 1H), 7.58-7.62 (m, 2H), 3.54-3.60 (m, 4H),3.34-3.38 (m, 2H), 2.59 (s, 3H), 2.32- 2.39 (m, 6H), 1.72-1.77 (m, 2H);LCMS (electrospray) m/z 458 (M + H)⁺. 297

Brown solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.20 (s, 1H), 8.34 (brs, 1H),8.07 (s, 1H), 8.05 (s, 1H), 7.58-7.61 (m, 2H), 3.41-3.46 (m, 2H), 2.59(s, 3H), 2.45-2.50 (m, 2H), 2.33- 2.40 (m, 4H), 1.46-1.53 (m, 4H),1.35-1.40 (m, 2H); LCMS (electrospray) m/z 441 (M + H)⁺. 298

Pale yellow solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.54 (s, 1H), 8.50 (s,1H), 8.21-8.23 (m, 1H), 8.01 (s, 1H), 7.93 (d, J = 8.8 Hz, 2H), 7.68 (d,J = 8.8 Hz, 2H), 7.15-7.18 (m, 1H), 3.65- 3.76 (m, 4H), 3.57-3.59 (m,1H), 3.18 (s, 3H), 2.92 (s, 3H), 2.36-2.39 (m, 1H), 2.26-2.28 (m, 1H);LCMS (electrospray) m/z 496 (M + H)⁺. 299

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.22 (s, 1H), 8.45 (d, J = 6.8Hz, 1H), 8.04-8.06 (m, 2H), 7.59-7.62 (m, 2H), 3.85-3.87 (m, 4H),3.30-3.35 (m, 1H), 2.59 (s, 3H), 1.93-1.96 (m, 2H), 1.47-1.49 (m, 2H);LCMS (electrospray) m/z 415 (M + H)⁺. 300

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 9.41 (s, 1H), 8.07 (s,1H), 7.26 (d, J = 8.8 Hz, 1H), 6.78 (d, J = 8.8 Hz, 1H), 3.78 (s, 3H),3.75 (s, 3H), 3.53 (s, 3H), 3.30-3.32 (m, 4H), 1.60-1.62 (m, 6H); LCMS(electrospray) m/z 433 (M + H)⁺. 301

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.24 (s, 1H), 8.68 (s,1H), 8.53 (s, 1H), 8.24-8.29 (m, 1H), 8.01 (s, 1H), 7.83 (d, J = 8.8 Hz,2H), 7.71 (d, J = 8.8 Hz, 2H), 7.32 (d, J = 8.8 Hz, 2H), 7.24-7.27 (m,1H), 7.99 (d, J = 8.8 Hz, 2H), 4.15-4.17 (m, 2H), 3.73-3.74 (m, 2H);LCMS (electrospray) m/z 524 (M + H)⁺. 302

Ivory solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.14 (s, 1H), 8.36 (s, 1H),8.04 (s, 1H), 7.68-7.73 (m, 2H), 7.14-7.21 (m, 2H), 3.53-3.61 (m, 4H),3.44-3.49 (m, 2H), 2.50-2.54 (m, 2H), 2.39-2.45 (m, 4H); LCMS(electrospray) m/z 406 (M + H)⁺. 303

Ivory solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.23 (s, 1H), 8.21 (brs, 1H),8.10 (s, 1H), 7.90 (d, J = 8.4 Hz, 2H), 7.78 (d, J = 8.4 Hz, 2H),3.53-3.58 (m, 4H), 3.43-3.48 (m, 2H), 2.49- 2.53 (m, 2H), 2.38-2.42 (m,4H); LCMS (electrospray) m/z 413 (M + H)⁺. 304

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.18 (s, 1H), 8.11 (s,1H), 7.72-7.74 (m, 1H), 7.70 (d, J = 8.8 Hz, 2H), 7.17 (d, J = 8.8 Hz,2H), 3.84-3.92 (m, 4H), 3.25-3.26 (m, 1H), 1.93 (s, 2H), 1.82-1.86 (m,2H), 1.40-1.49 (m, 2H), 0.94 (s, 9H); LCMS (electrospray) m/z 474 (M +H)⁺. 305

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.24 (s, 1H), 8.15 (s,1H), 8.05 (s, 1H), 7.73-7.75 (m, 1H), 7.58-7.63 (m, 2H), 3.87-3.93 (m,3H), 3.28-3.31 (m, 2H), 2.60 (s, 3H), 1.94 (s, 2H), 1.84-1.87 (m, 2H),1.43-1.51 (m, 2H), 0.95 (s, 9H); LCMS (electrospray) m/z 511 (M + H)⁺.306

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.30 (s, 1H), 8.61 (s,1H), 8.18 (s, 1H), 8.03 (d, J = 8.8 Hz, 2H), 7.98- 8.02 (m, 1H), 7.83(d, J = 8.8 Hz, 2H), 7.76-7.81 (m, 1H), 3.54-3.56 (m, 4H), 3.48-3.54 (m,4H), 1.42 (s, 9H); LCMS (electrospray) m/z 539 (M + H)⁺. 307

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.23 (s, 1H), 8.13 (s,1H), 8.04 (s, 1H), 7.56-7.61 (m, 2H), 3.93-3.96 (m, 2H), 3.15-3.20 (m,2H), 2.94 (s, 3H), 2.80 (s, 3H), 2.58 (s, 3H), 2.26-2.31 (m, 2H),2.00-2.02 (m, 1H), 1.77-1.80 (m, 2H), 1.22-1.30 (m, 2H); LCMS(electrospray) m/z 484 (M + H)⁺. 308

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.22 (s, 1H), 8.14 (s,1H), 8.05 (s, 1H), 7.58-7.63 (m, 2H), 3.70-3.74 (m, 1H), 3.58-3.60 (m,1H), 3.44-3.50 (m, 1H), 3.11-3.16 (m, 1H), 2.97 (s, 3H), 2.84 (s, 3H),2.65-2.73 (m, 1H0, 2.60 (s, 3H), 2.50-2.56 (m, 2H), 2.19-2.23 (m, 1H),1.73-1.78 (m, 1H); LCMS (electrospray) m/z 470 (M + H)⁺. 309

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.18 (s, 1H), 8.12 (s,1H), 7.69-7.73 (m, 2H), 7.16-7.20 (m, 2H), 3.61-3.69 (m, 3H), 3.51-3.57(m, 2H), 3.07 (s, 3H), 2.85 (s, 3H), 2.28-2.30 (m, 1H), 2.10-2.12 (m,1H); LCMS (electrospray) m/z 419 (M + H)⁺. 310

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.19 (s, 1H), 8.49-8.50 (m,1H), 8.07 (s, 1H), 7.69-7.72 (m, 2H), 7.15- 7.20 (m, 2H), 3.94 (brs,1H), 3.05-3.08 (m, 2H), 2.69-2.80 (m, 2H), 2.00-2.03 (m, 1H), 1.81-1.90(m, 1H), 1.51-1.63 (m, 3H); LCMS (electrospray) m/z 377 (M + H)⁺. 311

White solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.47 (brs, 1H), 7.93 (s,1H), 7.76-7.80 (m, 2H), 7.46 (brs, 1H), 7.07-7.12 (m, 2H), , 4.01-4.03(m, 1H), 2.45-2.46 (m, 1H), 2.20-2.32 (m, 4H), 1.58-1.62 (m, 2H),1.28-1.30 (m, 2H); LCMS (electrospray) m/z 391 (M + H)⁺. 312

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.13 (s, 1H), 8.37-8.39 (m,1H), 8.03 (s, 1H), 7.68-7.72 (m, 2H), 7.15- 7.19 (m, 2H), 3.68-3.70 (m,1H), 2.92-2.95 (m, 2H), 2.50- 2.53 (m, 2H), 1.89-1.91 (m, 2H), 1.34-1.37(m, 2H); LCMS (electrospray) m/z 377 (M + H)⁺. 313

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.14 (brs, 1H), 8.36 (d, J =6.8 Hz, 1H), 8.04 (s, 1H), 7.69-7.72 (m, 2H0, 7.15- 7.19 (m, 2H),3.61-3.63 (m, 1H), 2.70-2.73 (m, 2H), 2.16 (s, 3H), 1.88-2.03 (m, 4H),1.46-1.54 (m, 2H); LCMS (electrospray) m/z 391 (M + H)⁺. 314

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.13 (brs, 1H), 8.38 (d, J =7.2 Hz, 1H), 8.03 (s, 1H), 7.68-7.72 (m, 2H), 7.31- 7.35 (m, 2H),7.12-7.19 (m, 4H), 3.65-3.67 (m, 1H), 3.45 (s, 2H), 2.74-2.77 (m, 2H),2.05-2.11 (m, 2H), 1.94-1.97 (m, 2H), 1.45-1.53 (m, 2H); LCMS(electrospray) m/z 485 (M + H)⁺. 315

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.27 (s, 1H), 8.61 (s,1H), 8.16 (s, 1H), 8.03 (d, J = 8.8 Hz, 2H), 8.00- 8.01 (m, 1H), 7.83(d, J = 8.8 Hz, 2H), 7.78-7.80 (m, 1H), 3.44-3.47 (m, 4H), 2.79-2.81 (m,4H); LCMS (electrospray) m/z 439 (M + H)⁺. 316

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.19 (brs, 1H), 8.12 (s, 1H),7.68-7.71 (m, 2H), 7.14-7.18 (m, 2H), 6.65 (brs, 1H), 4.42-4.45 (m, 1H),3.87-3.90 (m, 1H), 3.59-3.65 (m, 1H), 3.17 (s, 3H); LCMS (electrospray)m/z 420 (M + H)⁺. 317

Pale yellow solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.59 (s, 1H), 8.54 (d,J = 2.8 Hz, 1H), 8.05-8.08 (m, 3H), 7.96-8.00 (m, 1H), 7.89 (d, J = 8.4Hz, 2H), 7.65-7.70 (m, 1H), 5.82 (brs, 1H), 4.63-4.65 (m, 1H), 4.07 (dd,J = 14.4, 3.2 Hz, 1H), 3.69 (dd, J = 14.4, 8.8 Hz, 1H), 3.30 (s, 3H);LCMS (electrospray) m/z 497 (M + H)⁺. 318

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.14 (brs, 1H), 8.50 (brs,1H), 8.03 (s, 1H), 7.67-7.71 (m, 2H), 7.14-7.18 (m, 2H), 6.94-7.04 (m,4H), 3.92-3.94 (m, 1H), 3.57-3.60 (m, 2H), 2.74-2.85 (m, 2H), 1.94-1.97(m, 1H), 1.78-1.80 (m, 1H), 1.62-1.65 (m, 1H), 1.50-1.55 (m, 1H); LCMS(electrospray) m/z 471 (M + H)⁺. 319

Pale yellow solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.41 (brs, 1H), 7.95(s, 1H), 7.77-7.80 (m, 4H), 7.59 (s, 1H), 7.3 (brs, 1H), 6.59 (s, 1H),3.91 (s, 3H), 3.58-3.61 (m, 6H), 2.64 (t, J = 6.0 Hz, 2H), 2.46-2.49 (m,4H); LCMS (electrospray) m/z 469 (M + H)⁺. 320

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.23 (s, 1H), 8.14 (s,1H), 8.04 (s, 1H), 7.58-7.59 (m, 2H), 6.88-6.93 (m, 2H), 6.58-6.61 (m,2H), 5.44-5.46 (m, 1H), 3.94-3.97 (m, 2H), 3.50-3.52 (m, 1H), 3.32-3.38(m, 2H), 2.58 (s, 3H), 1.99-2.03 (m, 2H), 1.43-1.45 (m, 2H); LCMS(electrospray) m/z 507 (M + H)⁺. 321

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.18 (s, 1H), 8.31-8.34(m, 1H), 8.05 (s, 1H), 8.03 (s, 1H), 7.58-7.61 (m, 2H), 3.42-3.46 (m,2H), 2.98 (s, 3H), 2.89-2.92 (m, 2H), 2.78 (s, 2H), 2.58 (s, 3H),2.51-2.55 (m, 3H), 1.96-2.02 (m, 2H), 1.53-1.58 (m, 4H); LCMS(electrospray) m/z 512 (M + H)⁺. 322

Ivory solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.19 (s, 1H), 8.12 (s, 1H),7.68-7.73 (m, 2H), 7.15-7.21 (m, 2H), 4.06- 4.11 (m, 1H), 3.88-3.93 (m,1H), 3.19-3.29 (m, 1H), 3.00- 3.10 (m, 2H), 2.87-2.95 (m, 1H), 2.16-2.24(m, 1H), 1.99- 2.12 (m, 2H), 1.82-1.89 (m, 1H), 1.67-1.77 (m, 2H), 1.34-1.40 (m, 1H); LCMS (electrospray) m/z 402 (M + H)⁺. 323

Ivory solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.25 (s, 1H), 8.15 (s, 1H),8.05 (s, 1H), 7.56-7.64 (m, 2H), 4.06-4.11 (m, 1H), 3.88-3.93 (m, 1H),3.19-3.29 (m, 1H), 3.00-3.08 (m, 2H), 2.87-2.95 (m, 1H), 2.59 (s, 3H),2.16-2.24 (m, 1H), 1.99-2.12 (m, 2H), 1.82-1.87 (m, 1H), 1.66-1.77 (m,2H), 1.34-1.40 (m, 1H); LCMS (electrospray) m/z 440 (M + H)⁺. 324

Ivory solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.29 (s, 1H), 8.62 (d, J = 2.0Hz, 1H), 8.18 (s, 1H), 8.00-8.05 (m, 3H), 7.77- 7.85 (m, 3H), 4.08-4.11(m, 1H), 3.90-3.94 (m, 1H), 3.19- 3.29 (m, 1H), 3.00-3.09 (m, 2H),2.88-2.95 (m, 1H), 2.17- 2.24 (m, 1H), 1.99-2.13 (m, 2H), 1.82-1.87 (m,1H), 1.66- 1.77 (m, 2H), 1.34-1.40 (m, 1H); LCMS (electrospray) m/z 479(M + H)⁺. 325

Ivory solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.25 (s, 1H), 8.62 (d, J = 2.4Hz, 1H), 8.36 (brs, 1H), 8.11 (s, 1H), 7.98- 8.06 (m, 3H), 7.77-7.86 (m,3H), 3.42-3.48 (m, 2H), 2.49- 2.54 (m, 2H), 2.37-2.46 (m, 4H), 2.27-2.35(m, 4H), 2.14 (s, 3H); LCMS (electrospray) m/z 497 (M + H)⁺. 326

Ivory solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.19 (s, 1H), 8.33 (brs, 1H),l8.07 (s, 1H), 8.04 (s, 1H), 3.43-3.47 (m, 2H), 2.59 (s, 3H), 2.49-2.54(m, 2H), 2.37-2.44 (m, 4H), 2.27- 2.34 (m, 4H), 2.14 (s, 3H); LCMS(electrospray) m/z 457 (M + H)⁺. 327

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.14 (s, 1H), 8.41 (brs, 1H),8.04 (s, 1H), 7.67-7.73 (m, 2H), 7.14-7.20 (m, 2H), 3.54-2.59 (m, 4H),3.30-3.34 (m, 2H), 2.30-2.38 (m, 6H), 1.71-1.77 (m, 2H); LCMS(electrospray) m/z 420 (M + H)⁺. 328

Ivory solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.24 (s, 1H), 8.62 (s, 1H),8.43 (brs, 1H), 8.10 (s, 1H), 7.98-8.11 (m, 3H), 7.78-7.85 (m, 3H),3.54-2.59 (m, 4H), 3.29-3.34 (m, 2H), 2.32-2.39 (m, 6H), 1.71-1.76 (m,2H); LCMS (electrospray) m/z 497 (M + H)⁺. 329

Ivory solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.23 (s, 1H), 8.55 (s, 1H),8.36 (brs, 1H), 8.25-8.30 (m, 1H), 8.10 (s, 1H), 7.85 (d, J = 8.8 Hz,2H), 7.72 (d, J = 8.8 Hz, 2H), 7.28 (d, J = 8.4 Hz, 1H), 3.42-3.47 (m,2H), 2.48-2.52 (m, 2H), 2.37- 2.42 (m, 4H), 1.46-1.51 (m, 4H), 1.36-1.41(m, 2H); LCMS (electrospray) m/z 482 (M + H)⁺. 330

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.18 (s, 1H), 8.65 (brt, J =5.2 Hz, 1H), 8.06 (s, 1H),l 7.69-7.72 (m, 2H), 7.18 (dd, J = 8.8, 8.8Hz, 2H), 6.64 (d, J = 6.4 Hz, 1H), 4.27- 4.29 (m, 1H), 3.71-3.74 (m,1H), 3.39-3.45 (m, 1H); LCMS (electrospray) m/z 406 (M + H)⁺. 331

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.19 (s, 1H), 8.12 (s, 1H),7.70-8.12 (m, 2H), 7.16-7.20 (m, 2H), 3.95- 3.98 (m, 2H), 3.16-3.22 (m,2H), 2.96 (s, 3H), 2.82 (s, 3H), 2.27-2.29 (m, 2H), 1.99-2.01 (m, 1H),1.79-1.82 (m, 2H), 1.23-1.30 (m, 2H); LCMS (electrospray) m/z 447 (M +H)⁺. 332

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.17 (s, 1H), 8.12 (s, 1H),7.69-7.73 (m, 2H), 7.16-7.20 (m, 2H), 3.69- 3.74 (m, 1H), 3.58-3.60 (m,1H), 3.46-3.50 (m, 1H), 3.11- 3.15 (m, 1H), 2.96 (s, 3H), 2.83 (s, 3H),2.65-2.70 (m, 1H), 2.50-2.60 (m, 2H), 2.19-2.23 (m, 1H), 1.73-1.78 (m,1H); LCMS (electrospray) m/z 433 (M + H)⁺. 333

Beige solid; ¹H NMR (400 MHz, acetone-d₆) δ 9.50 (s, 1H), 8.14 (s, 1H),7.95 (s, 1H), 7.64 (d, J = 8.4 Hz, 1H), 7.50 (d, J = 8.4 Hz, 1H), 7.43(s, 1H), 3.84-3.88 (m, 2H), 3.50-3.55 (m, 2H), 3.29-3.34 (m, 2H), 2.59(s, 3H), 1.65-1.68 (m, 5H), 1.25- 1.28 (m, 2H); LCMS (electrospray) m/z443 (M + H)⁺. 334

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.40 (s, 1H), 8.19 (s, 1H),7.71-7.74 (m, 2H), 7.18-7.22 (m, 2H), 5.07- 5.09 (m, 1H), 2.04-2.07 (m,2H), 1.70-1.74 (m, 2H), 1.55- 1.62 (m, 3H), 1.31-1.43 (m, 3H); LCMS(electrospray) m/z 377 (M + H)⁺. 335

Yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.86 (s, 1H), 8.42 (brs, 1H),8.38 (d, J = 2.8 Hz, 1H), 8.27 (s, 1H), 8.15 (dd, J = 8.8, 2.8 Hz, 1H),7.71-7.79 (m, 1H), 3.55-3.59 (m, 4H), 3.44-3.49 (m, 2H), 2.50-2.54 (m,2H), 2.38-2.43 (m, 4H); LCMS (electrospray) m/z 407 (M + H)⁺. 336

Ivory solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.25 (s, 1H), 8.15 (s, 1H),8.05 (s, 1H), 7.58-7.62 (m, 2H), 4.47 (brs, 1H), 3.52-3.56 (m, 6H), 2.60(s, 3H), 2.53-2.59 (m, 4H), 2.43- 2.48 (m, 2H); LCMS (electrospray) m/z444 (M + H)⁺. 337

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.30 (s, 1H), 8.55 (s, 1H),8.27-8.31 (m, 1H), 8.18 (s, 1H), 7.85 (d, J = 8.0 Hz, 2H), 7.73 (d, J =8.0 Hz, 2H), 7.28 (d, J = 8.4 Hz, 1H), 4.71 (brs, 1H), 3.52-3.56 (m,6H), 2.53-2.59 (m, 4H), 2.41-2.47 (m, 2H); LCMS (electrospray) m/z 483(M + H)⁺. 338

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.26 (s, 1H), 8.53 (s,1H), 8.24-8.29 (m, 1H), 8.16 (s, 1H), 7.84 (d, J = 8.4 Hz, 2H), 7.71 (d,J = 8.4 Hz, 2H), 7.25 (d, J = 8.4 Hz, 1H), 4.05-4.09 (m, 1H), 3.89-3.95(m, 1H), 3.19-3.26 (m, 1H), 3.00-3.09 (m, 2H), 2.86-2.93 (m, 1H),2.17-2.22 (m, 1H), 2.00-2.09 (m, 2H), 1.81-1.85 (m, 1H), 1.66-1.72 (m,2H), 1.34-1.39 (m, 1H); LCMS (electrospray) m/z 480 (M + H)⁺. 339

Pale yellowsolid; ¹H NMR (400 MHz, acetone-d₆) δ 9.59 (s, 1H), 8.50 (s,1H), 8.20-8.24 (m, 1H), 8.04 (s, 1H), 7.91 (d, J = 8.4 Hz, 2H), 7.67 (d,J = 8.4 Hz, 2H), 7.14-7.17 (m,l 1H), 5.80 (d, J = 6.4 Hz, 1H), 4.62-4.66(m, 1H), 4.06-4.12 (m, 1H), 3.69-3.75 (m, 1H), 3.29 (s, 3H); LCMS(electrospray) m/z 497 (M + H)⁺. 340

Orange solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.28 (s, 1H), 8.68 (brt, J =5.2 Hz, 1H), 8.62 (d, J = 1.6 Hz, 1H), 8.12 (s, 1H), 8.00-8.06 (m, 3H),7.78-7.85 (m, 3H), 6.65 (d, J = 6.4 Hz, 1H), 4.26-4.29 (m, 1H),3.71-3.75 (m, 1H), 3.27-3.35 (m, 1H); LCMS (electrospray) m/z 483 (M +H)⁺. 341

Yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.26 (s, 1H)_, 8.68 (brt, J =4.8 Hz, 1H), 8.55 (s, 1H), 8.26-8.30 (m, 1H), 811 (s, 1H), 7.83 (d, J =8.4 Hz, 2H), 7.71 (d, J = 8.4 Hz, 2H), 7.26 (dd, J = 8.0, 2.0 Hz, 1H),6.65 (d, J = 6.0 Hz, 1H), 4.27- 4.30 (m, 1H), 3.72-3.75 (m, 1H),3.40-3.46 (m, 1H); LCMS (electrospray) m/z 483 (M + H)⁺. 342

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.90 (s, 1H), 8.37 (s,1H), 8.33 (s, 1H), 8.12-8.15 (m, 1H), 7.74-7.79 (m, 1H), 3.44-3.46 (m,4H), 2.78-2.80 (m, 4H); LCMS (electrospray) m/z 363 (M + H)⁺. 343

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.17 (s, 1H), 8.14 (s,1H), 7.72-7.73 (m, 3H), 7.68-7.69 (m, 2H), 6.62-6.63 (m, 1H), 3.85 (s,3H), 3.31-3.46 (m, 4H), 2.78- 2.81 (m, 4H); LCMS (electrospray) m/z 424(M + H)⁺. 344

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 9.92 (s, 1H), 8.06 (s,1H), 7.49 (d, J = 8.8 Hz, 2H), 6.89 (d, J = 8.8 Hz, 2H), 3.57-3.60 (m,2H), 3.42-3.45 (m, 4H), 2.78-2.80 (m, 4H), 2.56-2.59 (m, 2H), 1.65-1.68(m, 2H), 1.43-1.47 (m, 1H), 1.16-1.26 (m, 2H), 0.91-0.93 (m, 3H); LCMS(electrospray) m/z 441 (M + H)⁺. 345

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.17 (s, 1H), 8.11 (s,1H), 7.72 (d, J = 8.8 Hz, 2H), 7.40 (d, J = 8.0 Hz, 2H), 7.00 (d, ,J =8.0 Hz, 2H), 6.99 (d, J = 8.8 Hz, 2H), 3.43- 3.46 (m, 4H), 2.78-2.81 (m,4H); LCMS (electrospray) m/z 470 (M + H)⁺. 346

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.25 (s, 1H), 8.46 (s,1H), 8.16 (s, 1H), 8.03-8.05 (m, 2H), 7.80-7.83 (m, 3H), 7.64-7.67 (m,1H), 3.44-3.47 (m, 4H), 2.79-2.81 (m, 4H), 2.31 (s, 3H); LCMS(electrospray) m/z 435 (M + H)⁺. 347

Pale brown solid; ¹H NMR (400 MHz, DMSO-d₆) δ 9.88 (s, 1H), 8.60 (s,1H), 7.99 (s, 1H), 7.48 (d, J = 9.2 Hz, 2H), 7.31 (d, J = 8.8 Hz, 2H),6.99 (d, J = 8.8 Hz, 2H), 6.88 (d, J = 9.2 Hz, 2H), 4.14 (t, J = 5.2 Hz,2H), 3.71-3.73 (m, 2H), 3.57-3.60 (m, 2H), 2.55-2.61 (m, 2H), 1.65-1.68(m, 2H), 1.45-1.46 (m, 1H), 1.16-1.26 (m, 2H), 0.91-0.93 (m, 3H); LCMS(electrospray) m/z 526 (M + H)⁺. 348

Pale brown solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.29 (s, 1H), 8.53 (s,1H), 8.26-8.27 (m, 1H), 8.17 (s, 1H), 7.84 (d, J = 8.8 Hz, 2H),7.74-7.76 (m, 1H), 7.71 (d, J = 8.8 Hz, 2H), 7.24- 7.27 (m, 1H),3.90-3.93 (m, 4H), 3.27-3.28 (m, 1H), 1.93 (s, 2H), 1.83-1.86 (m, 2H),1.44-1.46 (m, 2H), 0.94 (s, 6H); LCMS (electrospray) m/z 551 (M + H)⁺.349

Pale brown solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.29 (s, 1H), 8.61 (s,1H), 8.17 (s, 1H), 8.04 (d, J = 8.4 Hz, 2H), 7.99- 8.01 (m, 1H), 7.83(d, J = 8.4 Hz, 2H), 7.78-7.81 (m, 1H), 7.74-7.77 (m, 1H), 3.90-3.93 (m,4H), 3.27-3.28 (m, 1H), 1.93 (s, 2H), 1.83-1.86 (m, 2H), 1.44-1.46 (m,2H), 0.94 (s, 9H); LCMS (electrospray) m/z 551 (M + H)⁺. 350

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.26 (s, 1H), 8.55 (s, 1H),8.26-8.29 (m, 1H), 8.17 (s, 1H), 7.85 (d, J = 8.8 Hz, 2H), 7.72 (d, J =8.8 Hz, 2H), 7.26-7.28 (m, 1H), 3.71- 3.74 (m, 1H), 3.59-3.61 (m, 1H),3.47-3.49 (m, 1H), 3.12- 3.17 (m, 1H), 2.97 (s, 3H), 2.84 (s, 3H),2.67-2.69 (m, 1H), 2.53-2.60 (m, 2H), 2.20-2.22 (m, 1H), 1.75-1.77 (m,1H); LCMS (electrospray) m/z 510 (M + H)⁺. 351

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.27 (s, 1H), 8.55 (s, 1H),8.28-8.29 (m, 1H), 8.17 (s, 1H), 7.85 (d, J = 8.8 Hz, 2H), 7.72 (d, J =8.8 Hz, 2H), 7.26-7.28 (m, 1H), 3.95- 3.99 (m, 2H), 3.17-3.26 (m, 2H),2.96 (s, 3H), 2.82 (s, 3H), 2.27-2.29 (m, 2H), 1.99-2.02 (m, 1H),1.80-1.82 (m, 2H), 1.23-1.29 (m, 2H); LCMS (electrospray) m/z 524 (M +H)⁺. 352

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 9.95 (s, 1H), 8.06 (s, 1H),7.52 (d, J = 8.8 Hz, 2H), 6.90 (d, J = 8.8 Hz, 2H), 3.96-3.99 (m, 2H),3.70-3.72 (m, 4H), 3.21-3.24 (m, 2H), 3.04 (s, 3H), 3.03-3.06 (m, 4H),3.93-3.98 (m, 1H), 2.80 (s, 3H), 1.73-1.76 (m, 2H), 1.58-1.64 (m, 2H);LCMS (electrospray) m/z 500 (M + H)⁺. 353

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.12 (brs, 1H), 8.13 (s,1H), 7.63 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 3.96-3.99 (m,2H), 3.53-3.56 (m, 4H), 3.39 (s, 2H), 3.20-3.27 (m, 2H), 3.04 (s, 3H),2.93-2.99 (m, 1H), 2.80 (s, 3H), 2.30-2.34 (m, 4H), 1.73-1.76 (m, 2H),1.55-1.63 (m, 2H); LCMS (electrospray) m/z 514 (M + H)⁺. 354

Pale yellow solid; ¹H NMR (400 MHz, methanol-d₄) δ 8.42 (s, 1H),8.15-8.19 (m, 1H), 7.91 (s, 1H), 7.78 (d, J = 8.4 Hz, 2H), 7.61 (d, J =8.4 Hz, 2H), 7.11-7.13 (m, 1H), 4.13-4.16 (m, 1H), 3.59-3.61 (m, 1H),2.94-2.96 (m, 2H), 2.81 (s, 3H), 2.05-2.13 (m, 2H), 1.83-1.96 (m, 2H),1.64-1.68 (m, 1H); LCMS (electrospray) m/z 468 (M + H)⁺. 355

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.23 (s, 1H), 8.62-8.63(m, 1H), 8.35-8.36 (m, 1H), 8.10 (s, 1H), 8.06 (s, 1H), 8.04 (s, 1H),8.00-8.02 (m, 1H), 7.85 (s, 1H), 7.83 (s, 1H), 7.77-7.82 (m, 1H),3.46-3.47 (m, 2H), 3.00 (s, 3H), 2.91-2.93 (m, 2H), 2.80 (s, 3H),2.52-2.53 (m, 3H), 1.98-2.04 (m, 2H), 1.55-1.60 (m, 4H); LCMS(electrospray) m/z 553 (M + H)⁺. 356

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.19 (s, 1H), 8.36 (d, J = 7.2Hz, 1H), 8.04-8.06 (m, 2H), 7.60-7.63 (m, 2H), 4.43 (brs, 1H), 3.61-3.63(m, 1H), 2.70-2.73 (m, 2H), 2.59 (s, 3H), 2.16 (s, 3H), 1.93-2.03 (m,4H), 1.46-1.54 (m, 2H); LCMS (electrospray) m/z 428 (M + H)⁺. 357

White solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.18 (s, 1H), 8.38 (d, J = 7.2Hz, 1H), 8.04 (d, J = 7.2 Hz, 2H), 7.59-7.62 (m, 2H), 7.31-7.35 (m, 2H),7.12-7.16 (m, 2H), 3.65-3.68 (m, 1H), 3.45 (s, 2H), 2.74-2.77 (m, 2H),2.59 (s, 3H), 2.06- 2.11 (m, 2H), 1.94-1.97 (m, 2H), 1.46-1.54 (m, 2H);LCMS (electrospray) m/z 522 (M + H)⁺. 358

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.19 (s, 1H), 8.15 (s,1H), 7.77 (d, J = 8.8 Hz, 2H), 7.60-7.62 (m, 4H), 7.05 (d, J = 8.4 Hz,2H), 4.83 (s, 2H), 3.70-3.73 (m, 2H), 3.58- 3.61 (m, 3H), 3.28 (s, 3H),3.15 (s, 3H); LCMS (electrospray) m/z 478 (M + H)⁺. 359

Pale yellow solid; ¹H NMR (400 MHz, DMSO-d₆) δ 10.13 (s, 1H), 8.34 (brs,1H), 8.07 (s, 1H), 7.74 (d, J = 8.4 Hz, 2H), 7.58- 7.61 (m, 4H), 7.03(d, J = 8.4 Hz, 2H), 4.81 (s, 2H), 3.55- 3.57 (m, 5H), 3.45-3.46 (m,2H), 2.48-2.53 (m, 2H), 2.39- 2.42 (m, 4H); LCMS (electrospray) m/z 519(M + H)⁺. 360

¹H NMR (400 MHz, DMSO-d₆) δ 10.31 (s, 1H), 9.71 (brs, 1H), 8.59-8.63 (m,2H), 8.16 (s, 1H), 8.01-8.06 (m, 3H), 7.78- 7.85 (m, 3H), 3.99-4.02 (m,2H), 3.77-3.79 (m, 2H), 3.65- 3.71 (m, 2H), 3.51-3.54 (m, 2H), 3.40-3.42(m, 2H), 3.15- 3.18 (m, 2H), 2.37 (s, 6H).

TABLE 2 In vitro growth fluorescence assay (QUM) and intracellulargrowth assay (QIM) data of compounds 1-360 QUM QIM # cpds (MIC₅₀, uM)(MIC₅₀, uM) 1 + + 2 + + 3 ++ +++ 4 + + 5 + + 6 ++ ++ 7 + + 8 ++ ++ 9 + +10 + + 11 + + 12 + + 13 ++ +++ 14 ++ +++ 15 + + 16 + + 17 ++ + 18 ++ +19 ++ + 20 ++ + 21 + + 22 ++ ++ 23 + + 24 ++ + 25 + ++ 26 + + 27 + ++28 + ++ 29 ++ ++ 30 + N/D 31 + N/D 32 ++ +++ 33 + N/D 34 + N/D 35 ++++++ 36 ++ +++ 37 + + 38 ++ +++ 39 + +++ 40 ++ +++ 41 + +++ 42 ++ +++ 43++ +++ 44 + +++ 45 ++ +++ 46 ++ +++ 47 +++ +++ 48 +++ +++ 49 ++ +++ 50+++ +++ 51 ++ ++ 52 + ++ 53 +++ +++ 54 +++ +++ 55 + +++ 56 ++ ++ 57 ++++ 58 ++ +++ 59 + + 60 ++ ++ 61 ++ +++ 62 + ++ 63 + +++ 64 + ++ 65 + ++66 ++ +++ 67 ++ +++ 68 + +++ 69 + + 70 + + 71 + + 72 ++ +++ 73 + + 74+++ +++ 75 ++ + 76 +++ +++ 77 ++ +++ 78 +++ +++ 79 + +++ 80 ++ +++81 + + 82 + ++ 83 +++ +++ 84 +++ +++ 85 +++ +++ 86 +++ +++ 87 ++ ++88 + + 89 + + 90 +++ +++ 91 + +++ 92 ++ ++ 93 + + 94 + + 95 + +++ 96 ++++++ 97 ++ ++ 98 + + 99 ++ +++ 100 ++ +++ 101 ++ +++ 102 + + 103 +++ +++104 +++ +++ 105 ++ +++ 106 + +++ 107 + +++ 108 ++ +++ 109 + + 110 ++ +++111 ++ +++ 112 + +++ 113 + + 114 ++ +++ 115 ++ +++ 116 + ++ 117 + +118 + +++ 119 + +++ 120 +++ +++ 121 + +++ 122 +++ +++ 123 + + 124 ++++++ 125 +++ +++ 126 ++ + 127 +++ +++ 128 + + 129 ++ +++ 130 ++ +++131 + + 132 + +++ 133 ++ +++ 134 +++ +++ 135 ++ +++ 136 +++ +++ 137 +++++ 138 +++ +++ 139 ++ ++ 140 ++ ++ 141 + + 142 +++ +++ 143 +++ +++ 144+++ +++ 145 ++ +++ 146 ++ +++ 147 + + 148 + + 149 ++ ++ 150 + + 151 +++++ 152 ++ ++ 153 +++ +++ 154 +++ +++ 155 + +++ 156 ++ +++ 157 + + 158++ +++ 159 ++ +++ 160 + +++ 161 + +++ 162 ++ +++ 163 + + 164 + + 165 +++ 166 + + 167 ++ +++ 168 ++ +++ 169 ++ ++ 170 + + 171 + +++ 172 + +173 + + 174 ++ +++ 175 + + 176 + + 177 ++ +++ 178 ++ ++ 179 + + 180 +++++ 181 + + 182 + + 183 + +++ 184 + + 185 + + 186 + +++ 187 + + 188 ++++++ 189 + + 190 + + 191 + + 192 ++ ++ 193 + +++ 194 ++ +++ 195 + +++ 196++ ++ 197 + +++ 198 + + 199 ++ +++ 200 + + 201 +++ ++ 202 +++ +++ 203+++ +++ 204 +++ +++ 205 + + 206 + +++ 207 ++ +++ 208 +++ +++ 209 +++ +++210 + + 211 +++ +++ 212 ++ +++ 213 +++ +++ 214 + +++ 215 +++ +++ 216 ++++++ 217 ++ +++ 218 + +++ 219 ++ +++ 220 + +++ 221 ++ +++ 222 ++ +++ 223++ ++ 224 ++ +++ 225 ++ +++ 226 + +++ 227 ++ + 228 +++ +++ 229 + ++230 + + 231 +++ +++ 232 ++ +++ 233 ++ +++ 234 ++ +++ 235 + +++ 236 + +++237 +++ +++ 238 ++ +++ 239 ++ +++ 240 + +++ 241 + +++ 242 ++ +++ 243 ++++ 244 + +++ 245 ++ +++ 246 ++ +++ 247 ++ +++ 248 ++ +++ 249 + +++250 + +++ 251 ++ +++ 252 ++ +++ 253 N/D ++ 254 N/D +++ 255 N/D + 256 N/D+++ 257 N/D + 258 ++ +++ 259 N/D +++ 260 ++ +++ 261 +++ +++ 262 +++ +++263 + + 264 N/D ++ 265 +++ +++ 266 +++ +++ 267 ++ ++ 268 N/D +++ 269 + +270 + + 271 +++ +++ 272 +++ +++ 273 ++ +++ 274 ++ +++ 275 ++ +++ 276 ++++ 277 N/D +++ 278 N/D +++ 279 N/D ++ 280 N/D + 281 N/D ++ 282 N/D +++283 N/D +++ 284 +++ +++ 285 N/D +++ 286 N/D + 287 +++ +++ 288 +++ +++289 ++ +++ 290 + +++ 291 +++ +++ 292 ++ +++ 293 N/D +++ 294 + +++295 + + 296 ++ +++ 297 + ++ 298 +++ +++ 299 +++ +++ 300 N/D + 301 + +++302 ++ +++ 303 N/D + 304 + +++ 305 + +++ 306 + +++ 307 +++ +++ 308 ++++++ 309 ++ +++ 310 + + 311 + ++ 312 + + 313 + ++ 314 +++ +++ 315 ++ +++316 ++ +++ 317 ++ +++ 318 + +++ 319 ++ +++ 320 ++ +++ 321 + ++ 322 ++N/D 323 +++ +++ 324 +++ +++ 325 ++ +++ 326 + + 327 ++ ++ 328 +++ +++ 329++ +++ 330 ++ +++ 331 +++ +++ 332 +++ +++ 333 ++ +++ 334 ++ +++ 335 ++++ 336 ++ +++ 337 +++ +++ 338 +++ +++ 339 +++ +++ 340 ++ +++ 341 ++ +++342 ++ +++ 343 ++ +++ 344 ++ +++ 345 ++ +++ 346 ++ +++ 347 + + 348 + +++349 + +++ 350 +++ +++ 351 +++ +++ 352 +++ N/D 353 ++ N/D 354 ++ N/D 355++ N/D 356 + N/D 357 ++ N/D 358 +++ +++ 359 ++ +++ 360 +++ +++ Activityrange: +++ indicates <1 uM, ++ indicates between 1-20 uM, +indicates >20 uM

TABLE 3 Antibacterial activity of selected compounds # of cpd MDR-33MDR-137 MDR-146 83 +++ +++ +++ 127 +++ +++ +++ 144 +++ +++ +++ 202 ++++++ +++ MDR-33, 137 and 146: clinical isolates of multidrug-resistancetuberculosis Activity range: +++ indicates <2 times of MIC50 on wildtype strain (H37Rv), ++ indicates between 2 times and 5 times of MIC50on wild type strain (H37Rv), + indicates >5 times of MIC50 on wild typestrain (H37Rv)

1. A compound having the general formula I:

wherein n¹ and n² are independently 0, 1, 2, or 3; m is 0 or 1; A is amoiety selected from the group consisting of

R¹ is selected from the group consisting of hydrogen, halogen, C₁-C₁₀alkyl, C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl, hydroxyl, —OR³, —CN, —NO₂,—NH₂, —NR^(b)R^(c), aryl, heteroaryl and heterocyclyl wherein each ofsaid alkyl, cycloalkyl, aryl heteroaryl and heterocyclyl is optionallysubstituted with one to four R^(a) groups; R² is selected from the groupconsisting of hydrogen, halogen, C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl,C₁-C₃haloalkyl, hydroxyl, —OR³, —CN, —NO₂, —NH₂, —NR^(b)R^(c),—NR⁶C(O)R^(c), —(NR^(d))(V)_(p)R^(e), aryl, heteroaryl, heterocyclyl andgroups of formula Ia shown below, wherein each of said alkyl,cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substitutedwith one to four R^(a) groups;

wherein, o is independently, at each occurrence, 0, 1, 2 or 3; p is 0 or1, q is 0 or 1; X¹ is C═O, O, S, —S(O)₂—, —S(O)₂NR⁶—, —C(O)O—,—C(O)NR⁶—, —NHC(O)— or —(NR⁶)—; X² is CR^(b)R^(c), O, S, or NR⁶; Y isC₁-C₆ alkylene, O, S or NR⁶; V and W are independently, at eachoccurrence, C₁-C₆ alkylene; R³ is selected from the group consisting ofhydrogen, C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl, haloalkyl C₁-C₆alkyl-O-alkyl,C₂-C₁₀ alkenyl, C₃-C₁₀ cycloalkenyl, C₂-C₁₀ alkynyl, aryl, heteroaryland heterocyclyl, wherein each of said alkyl, cycloalkyl, aryl,heteroaryl and heterocyclyl is optionally substituted with one to fourR^(a) groups; R⁴ is selected from the group consisting of hydrogen,halogen, C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl, hydroxyl, —OR⁶,—CN, —NO₂, —NH₂, —NR^(b)R^(c), —N(R⁶)C(O)R⁶, —C(O)R⁶, —C(O)OR⁶,—C(O)NR^(b)R^(c), —S(O)R⁶, —S(O)₂R⁶, —S(O)₂NR^(b)R^(c), aryl, heteroaryland heterocyclyl wherein each of said alkyl, cycloalkyl, —OR⁶ aryl,heteroaryl and heterocyclyl is optionally substituted with one to fourR^(a) groups; R⁵ is selected from the group consisting of hydrogen,halogen, C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl, hydroxyl, —OR⁶,—CN, —NO₂, —NH₂, —NR^(b)R^(c), —N(R⁶)C(O)R⁶, —N(R⁶)C(O)OR⁶, —C(O)R⁶,—C(O)OR⁶, —C(O)NR^(b)R^(c), —CHOHR⁶, —S(O)R⁶, —S(O)₂R⁶,—S(O)₂NR^(b)R^(c), aryl, heteroaryl and heterocyclyl wherein each ofsaid alkyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl is optionallysubstituted with one to four R^(a) groups; R⁶ is independently, at eachoccurrence, selected from the group consisting of hydrogen, C₁-C₁₀alkyl, C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl, aryl, heteroaryl andheterocyclyl, wherein each of said alkyl, cycloalkyl, aryl, heteroaryland heterocyclyl is optionally substituted with one to four R^(a)groups; Z is selected from the group consisting of C₁-C₁₀ alkyl,C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl, OR⁷, aryloxy, aryl, heteroaryl,heterocyclyl, and groups of formula Ib shown below, wherein each of saidalkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl and groups of formulaIb is optionally substituted with one to four R^(a) groups;

wherein, p is 0 or 1; l is 1, 2 or 3; X³ is, independently at eachoccurrence, CH or N; X⁴ is C═O, CR^(b)R^(c), O, S, or NR⁷; R^(e), ifdenoted in formula Ib, may also occur twice as substituent at the samecarbon atom wherein R^(e) is independently selected at each occurrence;R^(a) is independently, at each occurrence, selected from the groupconsisting of hydrogen, halogen, C₁-C₃ alkyl, C₁-C₄ alkoxy, C₁-C₄ alkoxysubstituted with aryl, C₁-C₃ haloalkyl, hydroxyl, C₁-C₃ alkylhydroxyl,—CN, NO₂, —NR^(b)R^(c), —C(O)NR^(b)R^(c), —OR^(c), —C(O)R^(c),—C(O)OR^(c), sulfonyl, sulfoxide, C₃-C₁₀ cycloalkyl, heterocyclyl,heteroaryl and aryl, wherein each of said alkyl, cycloalkyl, aryl,heteroaryl and heterocyclyl is optionally substituted with one to fourC₁-C₃ alkyl, C₁-C₄ alkoxy, aryl, halogen, C₁-C₃ haloalkyl, hydroxyl,—NH₂, wherein such substitution, if present, may occur in such a mannerthat there is more than one substituent, per carbon atom, and whereinthese substituents may be the same or different; R^(b) and R^(c) areindependently, at each occurrence selected from the group consisting ofhydrogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₆ alkyl-O-alkyl, C₂-C₁₀alkenyl, C₁-C₄ alkoxy, C₁-C₃ alkylhydroxyl, C₃-C₁₀ cycloalkenyl, C₂-C₁₀alkynyl, C₁-C₁₀ haloalkyl, aryl, alkylaryl, heteroaryl, andheterocyclyl, wherein each of said alkyl, cycloalkyl, aryl, heteroaryland heterocyclyl is optionally substituted with one to four C₁-C₃ alkyl,C₁-C₄ alkoxy, halogen, aryloxy, C₁-C₃ haloalkyl, hydroxyl, C₁-C₃alkylhydroxyl, —CN, —NO₂, —NH₂, sulfonyl, sulfoxide, C₃-C₁₀ cycloalkyl,heterocyclyl, aryl, heteroaryl, wherein such substitution, if present,may occur in such a manner that there is more than one substituent percarbon atom, wherein such substituents may be the same or different; orR^(b) and R^(c) are connected to each other to make a four, five or sixmembered saturated or unsaturated cyclic or heterocyclic ring, or theyare connected to make a fused cyclic or heterocyclic ring structure;R^(d) is independently, at each occurrence, selected from the groupconsisting of hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl,aryl, heteroaryl and heterocyclyl, wherein each of said alkyl,cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substitutedwith one to four R^(a) groups; R^(e) is independently, at eachoccurrence, selected from the group consisting of hydrogen, halogen,C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃ haloalkyl, hydroxyl, —OR⁷, —CN,—(CH₂)_(l)R⁷, with l being 0, 1, 2 or 3, —NO₂, —NH₂, —NR^(b)R^(c),—N(R⁷)C(O)R⁷, —C(O)R⁷, —C(O)OR⁷, —C(O)NR^(b)R^(c), —S(O)R⁷, —S(O)₂R⁷,—S(O)₂NR^(b)R^(c), aryl, heteroaryl and heterocyclyl, wherein each ofsaid alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionallysubstituted with one to four R^(a) groups; R⁷ is independently, at eachoccurrence, selected from the group consisting of hydrogen, C₁-C₁₀alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃ haloalkyl, aryl, heteroaryl, andheterocyclyl, wherein each of said alkyl, cycloalkyl, aryl, heteroaryland heterocyclyl is optionally substituted with one to four R^(a)groups, and pharmaceutically acceptable salts thereof.
 2. The compoundaccording to claim 1 having the general formula II:

wherein n is 0, 1, 2 or 3; m is 0 or 1; o is 0, 1, 2 or 3; X² isCR^(b)R^(c), O, S, or NR⁶; Y is C₁-C₆ alkylene, O, S or NR⁶; R⁴ isselected from the group consisting of hydrogen, halogen, C₁-C₁₀ alkyl,C₃-C₁₀ cycloalkyl, C₁-C₃haloalkyl, hydroxyl, —OR⁶, —CN, —NO₂, —NH₂,—NR^(b)R^(c), —N(R⁶)C(O)R⁶, —C(O)R⁶, —C(O)OR⁶, —C(O)NR^(b)R^(c),—S(O)R⁶, —S(O)₂R⁶, —S(O)₂NR^(b)R^(c), aryl, heteroaryl and heterocyclylwherein each of said alkyl, cycloalkyl, aryl, heteroaryl andheterocyclyl is optionally substituted with one to four R^(a) groups; R⁶is independently, at each occurrence, selected from the group consistingof hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl, aryl,heteroaryl and heterocyclyl, wherein each of said alkyl, cycloalkyl,aryl, heteroaryl and heterocyclyl is optionally substituted with one tofour R^(a) groups; Z is selected from the group consisting of C₁-C₁₀alkyl, C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl, OR⁶, aryloxy, aryl, heteroaryl,heterocyclyl, and groups of formula Ib shown below, wherein each of saidalkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl and groups of formulaIb is optionally substituted with one to four R^(a) groups;

wherein, p is 0 or 1; l is 1, 2 or 3; X³ is, independently at eachoccurrence, CH or N; X⁴ is C═O, CR^(b)R^(c), O, S, or NR⁷; R^(e), ifdenoted in formula Ib, may also occur twice as substituent at the samecarbon atom wherein R^(e) is independently selected at each occurrence;R^(a) is independently, at each occurrence, selected from the groupconsisting of hydrogen, halogen, C₁-C₃ alkyl, C₁-C₄ alkoxy, alkoxysubstituted with aryl, aryloxy, C₁-C₃ haloalkyl, hydroxyl, C₁-C₃alkylhydroxyl, —CN, NO₂, —C(O)NR^(b)R^(c), —OR^(c), —C(O)R^(c),—C(O)OR^(c), sulfonyl, sulfoxide, C₃-C₁₀ cycloalkyl, heterocyclyl,heteroaryl and aryl, alkylaryl wherein each of said alkyl, cycloalkyl,aryl, heteroaryl and heterocyclyl is optionally substituted with one tofour C₁-C₃ alkyl, C₁-C₄ alkoxy, aryl, halogen, C₁-C₃ haloalkyl,hydroxyl, —NH₂ wherein such substitution, if present, may occur in sucha manner that there is more than one substituent, e.g. two or threesubstituents, per carbon atom, wherein such two or three substituentsmay be the same or different; R^(b) and R^(c) are, independently at eachoccurrence, selected from the group consisting of hydrogen, C₁-C₁₀alkyl, C₃-C₁₀ cycloalkyl, C₁-C₆ alkyl-O-alkyl, C₂-C₁₀ alkenyl, alkoxy,C₁-C₃ alkylhydroxyl, C₃-C₁₀ cycloalkenyl, C₂-C₁₀ alkynyl, C₁-C₁₀haloalkyl, aryl, alkylaryl, heteroaryl, and heterocyclyl, wherein eachof said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl isoptionally substituted with one to four C₁-C₃ alkyl, C₁-C₄ alkoxy,halogen, aryloxy, C₁-C₃ haloalkyl, hydroxyl, C₁-C₃ alkylhydroxyl, —CN,—NO₂, —NH₂, sulfonyl, sulfoxide, C₃-C₁₀ cycloalkyl, heterocyclyl, aryl,heteroaryl, wherein such substitution, if present, may occur in such amanner that there is more than one substituent, per carbon atom, whereinsuch substituents may be the same or different or they are connected tomake a fused cyclic or heterocyclic ring structure; or R^(b) and R^(c)are connected to each other to make a four, five or six memberedsaturated or unsaturated cyclic or heterocyclic ring, or they areconnected to make a fused cyclic or heterocyclic ring structure; R^(e)is independently, at each occurrence, selected from the group consistingof hydrogen, halogen, C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl, C₁-C₃ haloalkyl,hydroxyl, —OR⁷, —CN, —(CH₂)_(l)R⁷ with l being 0, 1, 2 or 3, —NO₂, —NH₂,—NR^(b)R^(c), —N(R⁷)C(O)R⁷, —C(O)R⁷, —C(O)OR⁷, —C(O)NR^(b)R^(c),—S(O)R⁷, —S(O)₂R⁷, —S(O)₂NR^(b)R^(c), aryl, heteroaryl and heterocyclyl,wherein each of said alkyl, cycloalkyl, aryl, heteroaryl andheterocyclyl is optionally substituted with one to four R^(a) groups; R⁷is independently, at each occurrence, selected from the group consistingof hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃ haloalkyl, aryl,heteroaryl and heterocyclyl, wherein each of said alkyl, cycloalkyl,aryl and heterocyclyl is optionally substituted with one to four R^(a)groups, and pharmaceutically acceptable salts thereof.
 3. The compoundaccording to claim 1 having the general formula III:

wherein n is 0, 1, 2 or 3; m is 0 or 1; o is 0, 1, 2 or 3; q is 0 or 1;X² is CR^(b)R^(c), O, S, or NR⁶; Y is C₁-C₆ alkylene, O, S or NR⁶; W isC₁-C₆ alkylene; R⁵ is selected from the group consisting of hydrogen,halogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃ haloalkyl, hydroxyl,—OR⁶, —CN, —NO₂, —NH₂, —NR^(b)R^(c), —N(R⁶)C(O)R⁶, —N(R⁶)C(O)OR⁶,—C(O)R⁶, —C(O)OR⁶, —C(O)NR^(b)R^(c), —CHOHR⁶, —S(O)R⁶, —S(O)₂R⁶,—S(O)₂NR^(b)R^(c), aryl, heteroaryl and heterocyclyl group wherein eachof said alkyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl isoptionally substituted with one to four R^(a) groups; R⁶ isindependently, at each occurrence, selected from the group consisting ofhydrogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃ haloalkyl, aryl,heteroaryl and heterocyclyl group, wherein each of said alkyl,cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substitutedwith one to four R^(a) groups; R⁸ is selected from the group consistingof hydrogen, halogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃ haloalkyl,hydroxyl, —OR⁹, —CN, —NO₂, —NH₂, aryl, heteroaryl and heterocyclyl groupwherein each of said alkyl, cycloalkyl, aryl, heteroaryl andheterocyclyl is optionally substituted with one to four R^(a) groups; R⁹is selected from the group consisting of C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl, C₁-C₃ haloalkyl, aryl, heteroaryl and heterocyclyl groupwherein each of said alkyl, cycloalkyl, aryl, heteroaryl andheterocyclyl is optionally substituted with one to four R^(a) groups; Zis selected from the group consisting of C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl, C₁-C₃ haloalkyl, OR⁶, aryloxy, aryl, heteroaryl,heterocyclyl, and groups of formula Ib shown below, wherein each of saidalkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl and groups of formulaIb is optionally substituted with one to four R^(a) groups;

wherein, p is 0 or 1; l is 1, 2 or 3; X³ is, independently at eachoccurrence, CH or N; X⁴ is C═O, CR^(b)R^(c), O, S, or NR⁷; R^(e), ifdenoted in formula Ib, may also occur twice as substituent at the samecarbon atom wherein R^(e) is independently selected at each occurrence;R^(a) is independently, at each occurrence, selected from the groupconsisting of hydrogen, halogen, C₁-C₃ alkyl, C₁-C₄ alkoxy, C₁-C₄ alkoxysubstituted with aryl, aryloxy, C₁-C₃ haloalkyl, hydroxyl, C₁-C₃alkylhydroxyl, —CN, NO₂, —NR^(b)R^(c), —C(O)NR^(b)R^(c), —OR^(c),—C(O)R^(c), —C(O)OR^(c), sulfonyl, sulfoxide, C₃-C₁₀ cycloalkyl,heterocyclyl, heteroaryl and aryl, benzyl, alkylaryl wherein each ofsaid alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionallysubstituted with one to four C₁-C₃ alkyl, C₁-C₄ alkoxy, halogen, C₁-C₃haloalkyl, hydroxyl, —NH₂ wherein such substitution, if present, mayoccur in such a manner that there is more than one substituent, percarbon atom, wherein such two or three substituents may be the same ordifferent; R^(b) and R^(c) are independently, at each occurrence,selected from the group consisting of hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl, C₁-C₆ alkyl-O-alkyl, C₂-C₁₀ alkenyl, C₁-C₄ alkoxy, C₁-C₃alkylhydroxyl, C₃-C₁₀ cycloalkenyl, C₂-C₁₀ alkynyl, C₁-C₁₀ haloalkyl,aryl, alkylaryl, heteroaryl, and heterocyclyl; wherein each of saidalkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionallysubstituted with one to four C₁-C₃ alkyl, C₁-C₄ alkoxy, halogen,aryloxy, C₁-C₃ haloalkyl, hydroxyl, C₁-C₃ alkylhydroxyl, —CN, —NO₂,—NH₂, sulfonyl, sulfoxide, C₃-C₁₀ cycloalkyl, heterocyclyl, aryl,heteroaryl, wherein such substitution, if present, may occur in such amanner that there is more than one substituent, per carbon atom, whereinsuch substituents may be the same or different; or R^(b) and R^(c) areconnected to each other to make a four, five or six membered saturatedor unsaturated cyclic or heterocyclic ring, or they are connected tomake a fused cyclic or heterocyclic ring structure; R^(e) isindependently, at each occurrence, selected from the group consisting ofhydrogen, halogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃ haloalkyl,hydroxyl, —OR⁷, —CN, —(CH₂)_(l)R⁷ with l being 0, 1, 2 or 3, —NO₂, —NH₂,—NR^(b)R^(c), —N(R⁷)C(O)R⁷, —C(O)R⁷, —C(O)OR⁷, —C(O)NR^(b)R^(c),—S(O)R⁷, —S(O)₂R⁷, —S(O)₂NR^(b)R^(c), aryl, heteroaryl and heterocyclylgroup, wherein each of said alkyl, cycloalkyl, aryl, heteroaryl andheterocyclyl is optionally substituted with one to four R^(a) groups; R⁷is independently, at each occurrence, selected from the group consistingof hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃ haloalkyl, aryl,heteroaryl, and heterocyclyl, wherein each of said alkyl, cycloalkyl,aryl, heteroaryl and heterocyclyl is optionally substituted with one tofour R^(a) groups, and pharmaceutically acceptable salts thereof.
 4. Thecompound according to claim 1 having the general formula IV:

wherein n is 0, 1, 2 or 3; m is 0 or 1; V is C₁-C₆ alkylene R¹⁰ andR^(d) are independently at each occurrence, selected from the groupconsisting of hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃haloalkyl, aryl, heteroaryl and heterocyclyl, wherein each of saidalkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionallysubstituted with one to four R^(a) groups; R^(e) is independently, ateach occurrence, selected from the group consisting of hydrogen,halogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃ haloalkyl, hydroxyl,—OR⁷, —CN, —(CH₂)_(l)R⁷ with l being 0, 1, 2 or 3, —NO₂, —NH₂,—NR^(b)R^(c), —N(R⁷)C(O)R⁷, —C(O)R⁷, —C(O)OR⁷, —C(O)NR^(b)R^(c),—S(O)R⁷, —S(O)₂R⁷, —S(O)₂NR^(b)R^(c), aryl, heteroaryl and heterocyclyl,wherein each of said alkyl, cycloalkyl, aryl, heteroaryl andheterocyclyl is optionally substituted with one to four R^(a) groups; R⁷is independently, at each occurrence, selected from the group consistingof hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃ haloalkyl, aryl,heteroaryl and heterocyclyl, wherein each of said alkyl, cycloalkyl,aryl, heteroaryl and heterocyclyl is optionally substituted with one tofour R^(a) groups; Z is selected from the group consisting of C₁-C₁₀alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃ haloalkyl, OR⁷, aryloxy, aryl,heteroaryl, heterocyclyl, and groups of formula Ib shown below, whereineach of said alkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl andgroups of formula Ib is optionally substituted with one to four R^(a)groups;

wherein, p is 0 or 1; l is 1, 2 or 3; X³ is, independently at eachoccurrence, CH or N; X⁴ is C═O, CR^(b)R^(c), O, S, or NR⁷; R^(e), ifdenoted in formula Ib, may also occur twice as substituent at the samecarbon atom wherein R^(e) is independently selected at each occurrence;R^(a) is independently, at each occurrence, selected from the groupconsisting of hydrogen, halogen, C₁-C₃ alkyl, C₁-C₄ alkoxy, C₁-C₄ alkoxysubstituted with aryl, aryloxy, C₁-C₃ haloalkyl, hydroxyl, C₁-C₃alkylhydroxyl, —CN, NO₂, —NR^(b)R^(c), —C(O)NR^(b)R^(c), —OR^(c),—C(O)R^(c), —C(O)OR^(c), sulfonyl, sulfoxide, C₃-C₁₀ cycloalkyl,heterocyclyl, heteroaryl and aryl, alkylaryl wherein each of said alkyl,cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substitutedwith one to four C₁-C₃ alkyl, C₁-C₄ alkoxy, aryl, halogen, C₁-C₃haloalkyl, hydroxyl, —NH₂, wherein such substitution, if present, mayoccur in such a manner that there is more than one substituent, percarbon atom, wherein such substituents may be the same or different;R^(b) and R^(c) are independently, at each occurrence, selected from thegroup consisting of hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃haloalkyl, C₁-C₆ alkyl-O-alkyl, C₂-C₁₀ alkenyl, C₁-C₄alkoxy, C₁-C₃alkylhydroxyl, C₃-C₁₀cycloalkenyl, C₂-C₁₀ alkynyl, C₁-C₁₀ haloalkyl,aryl, alkylaryl, heteroaryl, and heterocyclyl, wherein each of saidalkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionallysubstituted with one to four C₁-C₃ alkyl, C₁-C₄ alkoxy, halogen,aryloxy, C₁-C₃ haloalkyl, hydroxyl, C₁-C₃ alkylhydroxyl, —CN, —NO₂,—NH₂, sulfonyl, sulfoxide, C₃-C₁₀ cycloalkyl, heterocyclyl, aryl,heteroaryl, wherein such substitution, if present, may occur in such amanner that there is more than one substituent, per carbon atom, whereinsuch substituents may be the same or different; or R^(b) and R^(c) areconnected to each other to make a four, five or six membered saturatedor unsaturated cyclic or heterocyclic ring, or they are connected tomake a fused cyclic or heterocyclic ring structure; R^(d) isindependently, at each occurrence, selected from the group consisting ofhydrogen, C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl, aryl,heteroaryl and heterocyclyl group, wherein each of said alkyl,cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substitutedwith one to four R^(a) groups; R^(e) is independently, at eachoccurrence, selected from the group consisting of hydrogen, halogen,C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃ haloalkyl, hydroxyl, —OR⁷, —CN,—(CH₂)_(l)R⁷ with l being 0, 1, 2 or 3, —NO₂, —NH₂, —NR^(b)R^(c),—N(R⁷)C(O)R⁷, —C(O)R⁷, —C(O)OR⁷, —C(O)NR^(b)R^(c), —S(O)R⁷, —S(O)₂R⁷,—S(O)₂NR^(b)R^(c), aryl, heteroaryl and heterocyclyl group, wherein eachof said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl isoptionally substituted with one to four R^(a) groups; R⁷ isindependently, at each occurrence, selected from the group consisting ofhydrogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃ haloalkyl, aryl,heteroaryl, and heterocyclyl, wherein each of said alkyl, cycloalkyl,aryl, heteroaryl and heterocyclyl is optionally substituted with one tofour R^(a) groups, and pharmaceutically acceptable salts thereof.
 5. Thecompound according to claim 1, having one of the formulae 1-360, asshown in Tables 1-2.
 6. The compound according to claim 1, having aninhibitory activity on the growth of M. tuberculosis, inside amacrophage, at a concentration of less than 1 μM. 7-8. (canceled)
 9. Apharmaceutical composition comprising a compound according to claim 1,and a pharmaceutically acceptable carrier.
 10. A method of treatment ofa bacterial infection, comprising the application of a suitable amountof a compound according to claim 1 to a person in need thereof.
 11. Themethod according to claim 10, wherein said suitable amount is from 0.01mg/kg body weight to 1 g/kg body weight.
 12. A compound thatcompetitively inhibits the specific binding of a compound according toclaim 1, wherein such specific binding is with respect to a targetprotein of said compound.
 13. A pharmaceutical composition, comprising acompound according to claim 12, and a pharmaceutically acceptablecarrier.
 14. A method of treatment of a bacterial infection, comprisingthe application of a suitable amount of a compound according to claim12, to a person in need thereof.
 15. The compound, according to claim 5,having a formula selected from formulae 3, 6, 8, 13, 14, 17-20, 22, 24,25, 27-29, 32, 35, 36, 38-58, 60-68, 72, 74-80, 82-87, 90-92, 95-97,99-101, 103-108, 110-112, 114-116, 118-122, 124-127, 129, 130, 132-140,142-146, 149, 151-156, 158-162, 165, 167-169, 171, 174, 177, 178, 180,183, 186, 188, 192-197, 199, 201-204, 206-209, 211-229, 231-254, 256,258-262, 264-268, 271-279, 281-285, 287-294, 296-299, 301, 302, 304-309,311, 313-325, 327-346, 348-355, and 357-360 as shown in Tables 1-2. 16.The compound, according to claim 15, having a formula selected fromformulae 3, 13, 14, 32, 35, 36, 38-50, 53-55, 58, 61, 63, 66-68, 72, 74,76-80, 83-86, 90, 91, 95, 96, 99-101, 103-108, 110-112, 114, 115,118-122, 124, 125, 127, 129, 130, 132-138, 142-146, 151, 153-156,158-162, 167, 168, 171, 174, 177, 180, 183, 186, 188, 193-195, 197, 199,201-204, 206-209, 211-222, 224-226, 228, 231-252, 254, 256, 258-262,265, 266, 268, 271-278, 282-285, 287-294, 296, 298, 299, 301, 302,304-309, 314-320, 323-325, 328-334, 336-346, 348-352, and 358-360 asshown in Tables 1-2.
 17. The method, according to claim 10, wherein thebacterial infection is Tuberculosis.
 18. The method, according to claim14, wherein the bacterial infection is Tuberculosis.
 19. The method,according to claim 14, wherein the compound is selected from: a) acompound having the general formula

wherein n¹ and n² are independently 0, 1, 2, or 3; m is 0 or 1; A is amoiety selected from the group consisting of

R¹ is selected from the group consisting of hydrogen, halogen, C₁-C₁₀alkyl, C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl, hydroxyl, —OR³, —CN, —NO₂,—NH₂, —NR^(b)R^(c), aryl, heteroaryl and heterocyclyl wherein each ofsaid alkyl, cycloalkyl, aryl heteroaryl and heterocyclyl is optionallysubstituted with one to four R^(a) groups; R² is selected from the groupconsisting of hydrogen, halogen, C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl,C₁-C₃haloalkyl, hydroxyl, —OR³, —CN, —NO₂, —NH₂, —NR^(b)R^(c),—NR⁶C(O)R^(c), —(NR^(d))(V)_(p)R^(c), aryl, heteroaryl, heterocyclyl andgroups of formula Ia shown below, wherein each of said alkyl,cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substitutedwith one to four R^(a) groups;

wherein, o is independently, at each occurrence, 0, 1, 2 or 3; p is 0 or1, q is 0 or 1; X¹ is C═O, O, S, —S(O)₂—, —S(O)₂NR⁶—, —C(O)O—,—C(O)NR⁶—, —NHC(O)— or —(NR⁶)—; X² is CR^(b)R^(c), O, S, or NR⁶; Y isC₁-C₆ alkylene, O, S or NR⁶; V and W are independently, at eachoccurrence, C₁-C₆ alkylene; R³ is selected from the group consisting ofhydrogen, C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl, C₁-C₁₀ haloalkylC₁-C₆alkyl-O-alkyl, C₂-C₁₀ alkenyl, C₃-C₁₀ cycloalkenyl, C₂-C₁₀ alkynyl,aryl, heteroaryl and heterocyclyl, wherein each of said alkyl,cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substitutedwith one to four R^(a) groups; R⁴ is selected from the group consistingof hydrogen, halogen, C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl,hydroxyl, —OR⁶, —CN, —NO₂, —NH₂, —NR^(b)R^(c), —N(R⁶)C(O)R⁶, —C(O)R⁶,—C(O)OR⁶, —C(O)NR^(b)R^(c), —S(O)R⁶, —S(O)₂R⁶, —S(O)₂NR^(b)R^(c), aryl,heteroaryl and heterocyclyl wherein each of said alkyl, cycloalkyl, —OR⁶aryl, heteroaryl and heterocyclyl is optionally substituted with one tofour R^(a) groups; R⁵ is selected from the group consisting of hydrogen,halogen, C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl, hydroxyl, —OR⁶,—CN, —NO₂, —NH₂, —NR^(b)R^(c), —N(R⁶)C(O)R⁶, —N(R⁶)C(O)OR⁶, —C(O)R⁶,—C(O)OR⁶, —C(O)NR^(b)K—CHOHR⁶, —S(O)R⁶, —S(O)₂R⁶, —S(O)₂NR^(b)R^(c),aryl, heteroaryl and heterocyclyl wherein each of said alkyl,cycloalkyl, aryl, heteroaryl, and heterocyclyl is optionally substitutedwith one to four R^(a) groups; R⁶ is independently, at each occurrence,selected from the group consisting of hydrogen, C₁-C₁₀ alkyl,C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl, aryl, heteroaryl and heterocyclyl,wherein each of said alkyl, cycloalkyl, aryl, heteroaryl andheterocyclyl is optionally substituted with one to four R^(a) groups; Zis selected from the group consisting of C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl,C₁-C₃haloalkyl, OR⁷, aryloxy, aryl, heteroaryl, heterocyclyl, and groupsof formula Ib shown below, wherein each of said alkyl, cycloalkyl, aryl,heteroaryl, heterocyclyl and groups of formula Ib is optionallysubstituted with one to four R^(a) groups;

wherein, p is 0 or 1; l is 1, 2 or 3; X³ is, independently at eachoccurrence, CH or N; X⁴ is C═O, CR^(b)R^(c), O, S, or NR⁷; R^(e), ifdenoted in formula Ib, may also occur twice as substituent at the samecarbon atom wherein R^(e) is independently selected at each occurrence;R^(a) is independently, at each occurrence, selected from the groupconsisting of hydrogen, halogen, C₁-C₃ alkyl, C₁-C₄ alkoxy, alkoxysubstituted with aryl, C₁-C₃ haloalkyl, hydroxyl, C₁-C₃ alkylhydroxyl,—CN, NO₂, —NR^(b)R^(c), —C(O)NR^(b)R^(c), —OR^(c), —C(O)R^(c),—C(O)OR^(c), sulfonyl, sulfoxide, C₃-C₁₀ cycloalkyl, heterocyclyl,heteroaryl and aryl, wherein each of said alkyl, cycloalkyl, aryl,heteroaryl and heterocyclyl is optionally substituted with one to fourC₁-C₃ alkyl, C₁-C₄ alkoxy, aryl, halogen, C₁-C₃ haloalkyl, hydroxyl,—NH₂, wherein such substitution, if present, may occur in such a mannerthat there is more than one substituent, per carbon atom, wherein thesesubstituents may be the same or different; R^(b) and R^(c) areindependently, at each occurrence selected from the group consisting ofhydrogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₆ alkyl-O-alkyl, C₂-C₁₀alkenyl, C₁-C₄ alkoxy, C₁-C₃ alkylhydroxyl, C₃-C₁₀ cycloalkenyl, C₂-C₁₀alkynyl, C₁-C₁₀ haloalkyl, aryl, alkylaryl, heteroaryl, andheterocyclyl, wherein each of said alkyl, cycloalkyl, aryl, heteroaryland heterocyclyl is optionally substituted with one to four C₁-C₃ alkyl,C₁-C₄ alkoxy, halogen, aryloxy, C₁-C₃ haloalkyl, hydroxyl, C₁-C₃alkylhydroxyl, —CN, —NO₂, —NH₂, sulfonyl, sulfoxide, C₃-C₁₀ cycloalkyl,heterocyclyl, aryl, heteroaryl, wherein such substitution, if present,may occur in such a manner that there is more than one substituent percarbon atom, wherein such substituents may be the same or different; orR^(b) and R^(c) are connected to each other to make a four, five or sixmembered saturated or unsaturated cyclic or heterocyclic ring, or theyare connected to make a fused cyclic or heterocyclic ring structure;R^(d) is independently, at each occurrence, selected from the groupconsisting of hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃haloalkyl, aryl, heteroaryl and heterocyclyl, wherein each of saidalkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionallysubstituted with one to four R^(a) groups; R^(e) is independently, ateach occurrence, selected from the group consisting of hydrogen,halogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃ haloalkyl, hydroxyl,—OR⁷, —CN, —(CH₂)_(l)R⁷, with l being 0, 1, 2 or 3, —NO₂, —NH₂,—NR^(b)R^(c), —N(R⁷)C(O)R⁷, —C(O)R⁷, —C(O)OR⁷, —C(O)NR^(b)R^(c),—S(O)R⁷, —S(O)₂R⁷, —S(O)₂NR^(b)R^(c), aryl, heteroaryl and heterocyclyl,wherein each of said alkyl, cycloalkyl, aryl, heteroaryl andheterocyclyl is optionally substituted with one to four R^(a) groups; R⁷is independently, at each occurrence, selected from the group consistingof hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃ haloalkyl, aryl,heteroaryl, and heterocyclyl, wherein each of said alkyl, cycloalkyl,aryl, heteroaryl and heterocyclyl is optionally substituted with one tofour R^(a) groups, and pharmaceutically acceptable salts thereof; b) acompound having the general formula II:

wherein n is 0, 1, 2 or 3; m is 0 or 1; o is 0, 1, 2 or 3; X² isCR^(b)R^(c), O, S, or NR⁶; Y is C₁-C₆ alkylene, O, S or NR⁶; R⁴ isselected from the group consisting of hydrogen, halogen, C₁-C₁₀ alkyl,C₃-C₁₀ cycloalkyl, C₁-C₃ haloalkyl, hydroxyl, —OR⁶, —CN, —NO₂, —NH₂,—NR^(b)R^(c), —N(R⁶)C(O)R⁶, —C(O)R⁶, —C(O)OR⁶, —C(O)NR^(b)R^(c),—S(O)R⁶, —S(O)₂R⁶, —S(O)₂NR^(b)R^(c), aryl, heteroaryl and heterocyclylwherein each of said alkyl, cycloalkyl, aryl, heteroaryl andheterocyclyl is optionally substituted with one to four R^(a) groups; R⁶is independently, at each occurrence, selected from the group consistingof hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃ haloalkyl, aryl,heteroaryl and heterocyclyl, wherein each of said alkyl, cycloalkyl,aryl, heteroaryl and heterocyclyl is optionally substituted with one tofour R^(a) groups; Z is selected from the group consisting of C₁-C₁₀alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃ haloalkyl, OR⁶, aryloxy, aryl,heteroaryl, heterocyclyl, and groups of formula Ib shown below, whereineach of said alkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl andgroups of formula Ib is optionally substituted with one to four R^(a)groups;

wherein, p is 0 or 1; l is 1, 2 or 3; X³ is, independently at eachoccurrence, CH or N; X⁴ is C═O, CR^(b)R^(c), O, S, or NR⁷; R^(e), ifdenoted in formula Ib, may also occur twice as substituent at the samecarbon atom wherein R^(e) is independently selected at each occurrence;R^(a) is independently, at each occurrence, selected from the groupconsisting of hydrogen, halogen, C₁-C₃ alkyl, C₁-C₄ alkoxy, C₁-C₄ alkoxysubstituted with aryl, aryloxy, C₁-C₃ haloalkyl, hydroxyl, C₁-C₃alkylhydroxyl, —CN, NO₂, —C(O)NR^(b)R^(c), —OR^(c), —C(O)R^(c),—C(O)OR^(c), sulfonyl, sulfoxide, C₃-C₁₀ cycloalkyl, heterocyclyl,heteroaryl and aryl, alkylaryl wherein each of said alkyl, cycloalkyl,aryl, heteroaryl and heterocyclyl is optionally substituted with one tofour C₁-C₃ alkyl, C₁-C₄ alkoxy, aryl, halogen, C₁-C₃ haloalkyl,hydroxyl, —NH₂ wherein such substitution, if present, may occur in sucha manner that there is more than one substituent, e.g. two or threesubstituents, per carbon atom, wherein such two or three substituentsmay be the same or different; R^(b) and R^(c) are, independently at eachoccurrence, selected from the group consisting of hydrogen, C₁-C₁₀alkyl, C₃-C₁₀ cycloalkyl, C₁-C₆ alkyl-O-alkyl, C₂-C₁₀ alkenyl, C₁-C₄alkoxy, C₁-C₃ alkylhydroxyl, C₃-C₁₀ cycloalkenyl, C₂-C₁₀ alkynyl, C₁-C₁₀haloalkyl, aryl, alkylaryl, heteroaryl, and heterocyclyl, wherein eachof said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl isoptionally substituted with one to four C₁-C₃ alkyl, C₁-C₄ alkoxy,halogen, aryloxy, C₁-C₃ haloalkyl, hydroxyl, C₁-C₃ alkylhydroxyl, —CN,—NO₂, —NH₂, sulfonyl, sulfoxide, C₃-C₁₀ cycloalkyl, heterocyclyl, aryl,heteroaryl, wherein such substitution, if present, may occur in such amanner that there is more than one substituent, per carbon atom, whereinsuch substituents may be the same or different or they are connected tomake a fused cyclic or heterocyclic ring structure; or R^(b) and R^(c)are connected to each other to make a four, five or six memberedsaturated or unsaturated cyclic or heterocyclic ring, or they areconnected to make a fused cyclic or heterocyclic ring structure; R^(e)is independently, at each occurrence, selected from the group consistingof hydrogen, halogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃ haloalkyl,hydroxyl, —OR⁷, —CN, —(CH₂)_(l)R⁷ with l being 0, 1, 2 or 3, —NO₂, —NH₂,—NR^(b)R^(c), —N(R⁷)C(O)R⁷, —C(O)R⁷, —C(O)OR⁷, —C(O)NR^(b)R^(c),—S(O)R⁷, —S(O)₂R⁷, —S(O)₂NR^(b)R^(c), aryl, heteroaryl and heterocyclyl,wherein each of said alkyl, cycloalkyl, aryl, heteroaryl andheterocyclyl is optionally substituted with one to four R^(a) groups; R⁷is independently, at each occurrence, selected from the group consistingof hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃ haloalkyl, aryl,heteroaryl and heterocyclyl, wherein each of said alkyl, cycloalkyl,aryl and heterocyclyl is optionally substituted with one to four R^(a)groups, and pharmaceutically acceptable salts thereof; c) a compoundhaving the general formula III:

wherein n is 0, 1, 2 or 3; m is 0 or 1; o is 0, 1, 2 or 3; q is 0 or 1;X² is CR^(b)R^(c), O, S, or NR⁶; Y is C₁-C₆ alkylene, O, S or NR⁶; W isC₁-C₆ alkylene; R⁵ is selected from the group consisting of hydrogen,halogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃ haloalkyl, hydroxyl,—OR⁶, —CN, —NO₂, —NH₂, —NR^(b)R^(c), —N(R⁶)C(O)R⁶, —N(R⁶)C(O)OR⁶,—C(O)R⁶, —C(O)OR⁶, —C(O)NR^(b)R^(c), —CHOHR⁶, —S(O)R⁶, —S(O)₂R⁶,—S(O)₂NR^(b)R^(c), aryl, heteroaryl and heterocyclyl group wherein eachof said alkyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl isoptionally substituted with one to four R^(a) groups; R⁶ isindependently, at each occurrence, selected from the group consisting ofhydrogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃ haloalkyl, aryl,heteroaryl and heterocyclyl group, wherein each of said alkyl,cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substitutedwith one to four R^(a) groups; R⁸ is selected from the group consistingof hydrogen, halogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃ haloalkyl,hydroxyl, —OR⁹, —CN, —NO₂, —NH₂, aryl, heteroaryl and heterocyclyl groupwherein each of said alkyl, cycloalkyl, aryl, heteroaryl andheterocyclyl is optionally substituted with one to four R^(a) groups; R⁹is selected from the group consisting of C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl, aryl, heteroaryl and heterocyclyl groupwherein each of said alkyl, cycloalkyl, aryl, heteroaryl andheterocyclyl is optionally substituted with one to four R^(a) groups; Zis selected from the group consisting of C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl, C₁-C₃ haloalkyl, OR⁶, aryloxy, aryl, heteroaryl,heterocyclyl, and groups of formula Ib shown below, wherein each of saidalkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl and groups of formulaIb is optionally substituted with one to four R^(a) groups;

wherein, p is 0 or 1; l is 1, 2 or 3; X³ is, independently at eachoccurrence, CH or N; X⁴ is C═O, CR^(b)R^(c), O, S, or NR⁷; R^(e), ifdenoted in formula Ib, may also occur twice as substituent at the samecarbon atom wherein R^(e) is independently selected at each occurrence;R^(a) is independently, at each occurrence, selected from the groupconsisting of hydrogen, halogen, C₁-C₃ alkyl, C₁-C₄ alkoxy, C₁-C₄ alkoxysubstituted with aryl, aryloxy, C₁-C₃ haloalkyl, hydroxyl, C₁-C₃alkylhydroxyl, —CN, NO₂, —NR^(b)R^(c), —C(O)NR^(b)R^(c), —OR^(c),—C(O)R^(c), —C(O)OR^(c), sulfonyl, sulfoxide, C₃-C₁₀ cycloalkyl,heterocyclyl, heteroaryl and aryl, benzyl, alkylaryl wherein each ofsaid alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionallysubstituted with one to four C₁-C₃ alkyl, C₁-C₄ alkoxy, halogen, C₁-C₃haloalkyl, hydroxyl, —NH₂ wherein such substitution, if present, mayoccur in such a manner that there is more than one substituent, percarbon atom, wherein such substituents may be the same or different;R^(b) and R^(c) are independently, at each occurrence, selected from thegroup consisting of hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₆alkyl-O-alkyl, C₂-C₁₀ alkenyl, C₁-C₄ alkoxy, C₁-C₃ alkylhydroxyl, C₃-C₁₀cycloalkenyl, C₂-C₁₀ alkynyl, C₁-C₁₀ haloalkyl, aryl, alkylaryl,heteroaryl, and heterocyclyl; wherein each of said alkyl, cycloalkyl,aryl, heteroaryl and heterocyclyl is optionally substituted with one tofour C₁-C₃ alkyl, C₁-C₄ alkoxy, halogen, aryloxy, C₁-C₃ haloalkyl,hydroxyl, C₁-C₃ alkylhydroxyl, —CN, —NO₂, —NH₂, sulfonyl, sulfoxide,C₃-C₁₀ cycloalkyl, heterocyclyl, aryl, heteroaryl, wherein suchsubstitution, if present, may occur in such a manner that there is morethan one substituent, per carbon atom, wherein such substituents may bethe same or different; or R^(b) and R^(c) are connected to each other tomake a four, five or six membered saturated or unsaturated cyclic orheterocyclic ring, or they are connected to make a fused cyclic orheterocyclic ring structure; R^(e) is independently, at each occurrence,selected from the group consisting of hydrogen, halogen, C₁-C₁₀ alkyl,C₃-C₁₀ cycloalkyl, C₁-C₃ haloalkyl, hydroxyl, —OR⁷, —CN, —(CH₂)_(l)R⁷with l being 0, 1, 2 or 3, —NO₂, —NH₂, —NR^(b)R^(c), —N(R⁷)C(O)R⁷,—C(O)R⁷, —C(O)OR⁷, —C(O)NR^(b)R^(c), —S(O)R⁷, —S(O)₂R⁷,—S(O)₂NR^(b)R^(c), aryl, heteroaryl and heterocyclyl group, wherein eachof said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl isoptionally substituted with one to four R^(a) groups; R⁷ isindependently, at each occurrence, selected from the group consisting ofhydrogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃ haloalkyl, aryl,heteroaryl, and heterocyclyl, wherein each of said alkyl, cycloalkyl,aryl, heteroaryl and heterocyclyl is optionally substituted with one tofour R^(a) groups, and pharmaceutically acceptable salts thereof; and d)a compound having the general formula IV:

wherein n is 0, 1, 2 or 3; m is 0 or 1; V is C₁-C₆ alkylene R¹⁰ andR^(d) are independently at each occurrence, selected from the groupconsisting of hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl,aryl, heteroaryl and heterocyclyl, wherein each of said alkyl,cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substitutedwith one to four R^(a) groups; R^(e) is independently, at eachoccurrence, selected from the group consisting of hydrogen, halogen,C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl, hydroxyl, —OR⁷, —CN,—(CH₂)_(l)R⁷ with l being 0, 1, 2 or 3, —NO₂, —NH₂, —NR^(b)R^(c),—N(R⁷)C(O)R⁷, —C(O)R⁷, —C(O)OR⁷, —C(O)NR^(b)R^(c), —S(O)R⁷, —S(O)₂R⁷,—S(O)₂NR^(b)R^(c), aryl, heteroaryl and heterocyclyl, wherein each ofsaid alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionallysubstituted with one to four R^(a) groups; R⁷ is independently, at eachoccurrence, selected from the group consisting of hydrogen, C₁-C₁₀alkyl, C₃-C₁₀cycloalkyl, C₁-C₃ haloalkyl, aryl, heteroaryl andheterocyclyl, wherein each of said alkyl, cycloalkyl, aryl, heteroaryland heterocyclyl is optionally substituted with one to four R^(a)groups; Z is selected from the group consisting of C₁-C₁₀ alkyl,C₃-C₁₀cycloalkyl, C₁-C₃ haloalkyl, OR⁷, aryloxy, aryl, heteroaryl,heterocyclyl, and groups of formula Ib shown below, wherein each of saidalkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl and groups of formulaIb is optionally substituted with one to four R^(a) groups;

wherein, p is 0 or 1; l is 1, 2 or 3; X³ is, independently at eachoccurrence, CH or N; X⁴ is C═O, CR^(b)R^(c), O, S, or NR⁷; R^(e), ifdenoted in formula Ib, may also occur twice as substituent at the samecarbon atom wherein R^(e) is independently selected at each occurrence;R^(a) is independently, at each occurrence, selected from the groupconsisting of hydrogen, halogen, C₁-C₃ alkyl, C₁-C₄ alkoxy, C₁-C₄ alkoxysubstituted with aryl, aryloxy, C₁-C₃ haloalkyl, hydroxyl, C₁-C₃alkylhydroxyl, —CN, NO₂, —NR^(b)R^(c), —C(O)NR^(b)R^(c), —OR^(e),—C(O)R^(c), —C(O)OR^(c), sulfonyl, sulfoxide, C₃-C₁₀ cycloalkyl,heterocyclyl, heteroaryl and aryl, alkylaryl wherein each of said alkyl,cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substitutedwith one to four C₁-C₃ alkyl, C₁-C₄ alkoxy, aryl, halogen, C₁-C₃haloalkyl, hydroxyl, —NH₂, wherein such substitution, if present, mayoccur in such a manner that there is more than one substituent, percarbon atom, wherein such substituents may be the same or different;R^(b) and R^(c) are independently, at each occurrence, selected from thegroup consisting of hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃haloalkyl, C₁-C₆ alkyl-O-alkyl, C₂-C₁₀ alkenyl, C₁-C₄alkoxy, C₁-C₃alkylhydroxyl, C₃-C₁₀cycloalkenyl, C₂-C₁₀ alkynyl, C₁-C₁₀ haloalkyl,aryl, alkylaryl, heteroaryl, and heterocyclyl, wherein each of saidalkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionallysubstituted with one to four C₁-C₃ alkyl, C₁-C₄ alkoxy, halogen,aryloxy, C₁-C₃ haloalkyl, hydroxyl, C₁-C₃ alkylhydroxyl, —CN, —NO₂,—NH₂, sulfonyl, sulfoxide, C₃-C₁₀ cycloalkyl, heterocyclyl, aryl,heteroaryl, wherein such substitution, if present, may occur in such amanner that there is more than one substituent, per carbon atom, whereinsuch substituents may be the same or different; or R^(b) and R^(c) areconnected to each other to make a four, five or six membered saturatedor unsaturated cyclic or heterocyclic ring, or they are connected tomake a fused cyclic or heterocyclic ring structure; R^(d) isindependently, at each occurrence, selected from the group consisting ofhydrogen, C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl, aryl,heteroaryl and heterocyclyl group, wherein each of said alkyl,cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substitutedwith one to four R^(a) groups; R^(e) is independently, at eachoccurrence, selected from the group consisting of hydrogen, halogen,C₁-C₁₀ alkyl, C₃-C₁₀cycloalkyl, C₁-C₃haloalkyl, hydroxyl, —OR⁷, —CN,—(CH₂)_(l)R⁷ with l being 0, 1, 2 or 3, —NO₂, —NH₂, —NR^(b)R^(c),—N(R⁷)C(O)R⁷, —C(O)R⁷, —C(O)OR⁷, —C(O)NR^(b)R^(c), —S(O)R⁷, —S(O)₂R⁷,—S(O)₂NR^(b)R^(c), aryl, heteroaryl and heterocyclyl group, wherein eachof said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl isoptionally substituted with one to four R^(a) groups; R⁷ isindependently, at each occurrence, selected from the group consisting ofhydrogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₃ haloalkyl, aryl,heteroaryl, and heterocyclyl, wherein each of said alkyl, cycloalkyl,aryl, heteroaryl and heterocyclyl is optionally substituted with one tofour R^(a) groups, and pharmaceutically acceptable salts thereof. 20.The method, according to claim 14, wherein the compound has a formulaselected from formulae 3, 6, 8, 13, 14, 17-20, 22, 24, 25, 27-29, 32,35, 36, 38-58, 60-68, 72, 74-80, 82-87, 90-92, 95-97, 99-101, 103-108,110-112, 114-116, 118-122, 124-127, 129, 130, 132-140, 142-146, 149,151-156, 158-162, 165, 167-169, 171, 174, 177, 178, 180, 183, 186, 188,192-197, 199, 201-204, 206-209, 211-229, 231-254, 256, 258-262, 264-268,271-279, 281-285, 287-294, 296-299, 301, 302, 304-309, 311, 313-325,327-346, 348-355, and 357-360 as shown in Tables 1-2.